Synthon

Working too much

2011-06-25T14:35:00.000-07:00

There's a certain sort of cocky first year, which both my boyfriend and I were (are? when am I considered a second year?) that starts off thinking that you can work in lab sustainably 7 days a week. As an undergrad, I essentially did that--7 days a week I was either studying or in lab, pretty much constantly working except Friday and Saturday night.

Well there are numerous, copious differences between graduate school and undergrad, most of which won't be touched upon here (like the difference between it being your job to produce results and having research be strictly pedagogical, which is a big one). But one large thing that I didn't factor in was the existence of long winter breaks and summer breaks. Summers I was working in labs, but I always took at least a couple weeks off on either end of the summer, and I generally was working a 9-6, five days a week schedule because I needed someone to supervise me who didn't want to be around on the weekends and evenings. Winter break was a good 5 weeks long, and the only winter I spent most of it working was my senior year (and even then I took a good 2 weeks off around Christmas). So you can sustainably work full throttle, because you are really only doing it for 4 month chunks.

Well in graduate school, I get 2 weeks off for vacation. There are times when I need to work full throttle...when things are going well, or last semester during midterms/finals when stuff started to pile up. There are times when your personal life goes to shit and you immerse yourself in work to escape how shitty your life has become. But there aren't these long recuperative breaks. It's no longer this 4 month sprint, dictated by the semesters (as much...there's still a bit of that); it's continual. You need to work sustainably.

So the older students are right, generally if you take one day off a week to spend doing something not lab-related, you are more productive and happier and more able to work all out during the normal work-week. And it's not because they lack the same enthusiasm for what they do, but just that they know what is sustainable and what is not. And we are not special. Everyone starts out that way. It's just the way things go.

2011-04-07T18:40:00.001-07:00

I got my NSF comment sheets, and it sort of sent me into a set of blues. No, it's not that I'm bent out of shape about not winning an absurdly competitive fellowship...it's about the frustration with myself that I'm good but just not good enough to be excellent. I knew that in applying, seeing my friend who has done teach for America in rural Mississippi, has 2 papers and 2 poster presentations, a Goldwater, and an absurd GPA and reading her essays along with seeing her qualifications that I just am not that awesome. I don't know how to change the fact that I don't have any publications...I don't think this problem will persist throughout my graduate career, but I also don't have a project that's a hit and run with it project right now and it's going to take a little bit of patience to get some of my shit to work. Like maybe a year. I don't know. Maybe things will start rolling this summer after classes are done. But it's just not bam bam bam falling into place for me immediately. Immediacy is rewarded in science sometimes (at least for the $$$), even if some of the most meaningful results are on a longer timescale and you have to fight for them more.

I've never been a fit the mold awesome student, and I've always ridden off of giving people the impression that I am passionate, competent, and possess skills that don't manifest themselves in the classroom but are ultimately the skills a scientist needs. But even this has yet to manifest itself in a publication (in my first year of graduate school) and while I'm trying to keep this all in perspective...well... Perhaps it's the fact that I keep the company of too many over achievers. My best friend is submitting his first first-authored paper to a high impact journal in his second semester of grad school. It makes me feel like, well, WTF am I doing with my life?

For my reviews I got a Good/Very Good and Very Good/Good. I know in this game, Good isn't Good enough; you have to be Excellent and Very Good. Actually, my weak academic record and lack of a publication record wasn't even commented on (although one reviewer commented that I didn't have any abstract or poster presentations). Actually the reviewers really had nothing but nice, even glowing things to say in the comment sheet. The only negative thing (besides the comment about poster presentations) was that my previous research statement could have more details in it (how could I fit any more details in 2 pages?). All the rest of the comments were on how strong and well written my proposed research was; how I had varied research; how my research in natural products carried into my future research; how my personal statement was good; how strong my letters were (and how one in particular said that I had incredible enthusiasm for science and potential for future success); how I demonstrated a commitment to outreach to elementary schools; how I demonstrated a commitment to mentoring undergraduates; how my international research experience is a positive indicator for collaborative networks and broad dissemination in my field; how I explained how my work is relevant to the scientific community at large.

Really these rating sheets are pretty much useless. They say that I'm a good scientist and have a lot of potential, but I am just not awesome enough to be competitive for awesome people fellowships for awesome people who deserve to get awesome amounts of money. I guess I should take it as a complement that I got this far?

2011-03-13T15:11:00.001-07:00

Oh my goodness, I cannot wait to be done with classes. It's spring break and I'm finally getting a chance to re-channel 100% of my focus to research, and it is glorious. Even if my experiments aren't working (yet).

First year graduate student

2011-02-20T10:15:00.000-08:00

When I was in Germany, at no point of their education did people ever juggle the way they do in the US.

Take my senior thesis. While doing my senior thesis, I was applying to grad school, taking a few classes, TAing a section of o-chem, and doing individual tutoring at the tutoring center. Take the first year of grad school. I'm TAing, taking 2-3 classes, and doing research. For the past two years, I've had lab as a first priority, squeezed in (in nights, weekends, and mornings primarily) between taking classes, teaching classes, grading, doing homework, and attending meetings. It's only been summers where my whole and entire focus can be dedicated to research.

In Germany, people didn't do an undergrad thesis, but they did do a diploma thesis (sort of like masters). Their diploma thesis was done in 6-9 months after they finished all their coursework. Their PhD was nothing but research. There was none of this frantic racing around, setting up that reaction before you had to run off to TA, sending a text asking a labmate to induce your cells while you're in class.

I suppose some first years handle it differently, making research less of a priority until they hit their second year, mainly just focusing on their classes. That's not why I went to grad school.

And on top of all the trying to get that experiment in, trying to finish your group meeting presentation, trying to stay on top of classes, I also feel obligated (and want) to do all the things I know are good to do. I want to go to at least a seminar or two every week. I want to stay on top of the literature--both in my specific field, and broadly in chemistry. I want to go to lunch with seminar speakers. I did this as an undergrad...I should be able to do this now, right? Right?

I love knowledge. I know classes are giving me knowledge, and I appreciate that. I guess I won't appreciate the influence they have on me until later--in terms of how I think about chemistry as is the pattern with classes. I guess I definitely got something out of both of the classes I took last fall, one in particular. But I dunno, I've been taking classes for so long, and I know that I will never have a chance to take a class in every area of chemistry that I'm interested in. I think I'm ready to pick up knowledge in less structured formats, as I need/want to know it. Luckily after this summer, I will never need to take a class again.

I wonder if this juggling game they put you through in grad school as a first year PhD student prepares you better for modern academia. I watch my PI, and he's split between so many obligations...

And then there's teaching. I enjoy teaching. There was this moment in my office hour last week when I coached someone through an equilibrium expression, and I thought "wow, this is satisfying." I do think it's valuable to force me to recall very fundamental chemistry that I don't encounter day-to-day. But I also see my friends on RA and how much they are able to accomplish in lab without dividing their attention constantly, and it's frustrating.

I don't know which of my (too many) projects are going to hit.

What am I doing with my life, anyway?

2010-10-28T18:54:00.000-07:00

These days I'm a graduate student, and I'm finding that I have less and less time to post.

I'm doing well; my research hasn't made any obvious, tangible progress yet, but I'm slowly getting there...working on it bit by bit. I have a great group and a great boss and really that seems to make all the difference. The classes are going ok and TAing is fine, but I'm just swamped with work to do all the time as is the graduate student lifestyle.

2010-06-12T13:48:00.000-07:00

The more I read about the field I'm studying in grad school, the more I realize that my knowledge of this field is so ridiculously small.

It's not that I didn't expect this to be the case. Generally the more you learn, the more overwhelmed you are by how much you just don't know.

But these systems all have a lot of nuance, and it's a lot to wrap my head around. I assume much of the details will become second nature as I dive into projects and am surrounded by the terminology in lab meetings and have been reading these papers for many years...but as it stands I realize that I just don't know much at all.

2010-06-11T12:47:00.000-07:00

In the past all my projects have been constrained by time; usually a summer, a semester, or (for my undergraduate thesis) an academic school year. This means that there is very little to loose, because it's obscene to expect that anyone gets results in 3-9 months. If you do, you're lucky. If you don't, you learn from the experience and that's what it's mainly about anyway at the undergraduate level.

Graduate school is going to be different, though. In graduate school, there's going to be time to see through a project to completion. I'm not going to abandon my babies half-finished. Of course, there's the whole idea of never really completing a project...and always having a follow-up project, but there will be five, maybe more years to make it work. And this is exciting and scary, because you never really have the excuse "oh I didn't have enough time to make it work."

It either gets finished or abandoned, I guess.

2010-06-10T20:10:00.000-07:00

One of the few ways I know how to lift myself out of depression is to go to lab.

Of course, this strategy is somewhat less effective if you're working and working and never seeing any results...but even the act of working towards a result can help me sometimes.

I was feeling overwhelmed about various personal things in my life, many of them related to anxieties about moving and starting a new phase in my life. Right now I'm kind of still working in my undergrad lab in a very low-expectation, lackadaisical kind of way, and I very nearly didn't go in at all because I was feeling kind of shitty.

I finally got up the energy to go in at around 3 pm to check up on some stuff, and I realized a ligation had worked when I screened it by PCR. It was one of those surprise ligations where only one colony on the plate grows, but that one transformant is the right transformat. It was enough to lift me out of my funk.

So...after dinner I came back and started working on this more. Re-doing the ligation that didn't work, and transforming the miniprep of the ligation that did work into an expression strain. I'm going to be here until 10 pm. It's totally illogical for me to be working like this. I should be coming in at 9 like a normal person. And for that matter, even if I do get a soluble expression of this protein, I'm leaving town in less than two weeks. There's not enough time for me to play with this.

But I can't help myself. I have to do that transformation. I have to see.

It's an addiction.

2010-03-05T17:04:00.001-08:00

So one thing that I've run into lately in applying to graduate school and trying to decide where to go next year is that--because I'm interested in natural product biosynthesis, especially polyketides--this has made my search for a lab a lot more focused than many people in that in general, I'm looking at specific PIs and specific labs. None of the places I'm considering has more than one or two people who do what I want to do.

I find that I have to defend my interests a lot. "Are you really not going to get sick of polyketides?"

This weirds me out in some ways because really what fascinates me about science are the questions. Of course I like going in lab and trying to troubleshoot problems and I like working with my hands, but I don't feel wedded to techniques which I have always been able to pick up as they are required and which are constantly changing anyway. If I were to say "I'm sure I want to be a crystallographer" or "I'm sure I want to be a synthetic organic chemist" I don't think anyone would question me as much as people do right now. I want to do any techniques I can to explore the chemical/biochemical questions I'm interested in--which is how can nature effect such fantastic chemistry with such extreme stereocontrol from very simple molecules in a modular fashion? How are these small molecules that have captured organic chemists' fascination from the start synthesized? How can we learn the "rules" of biological catalysis for small molecules?

There's a lot of chemical biology out there that I think is just gimmicky crap. This is one of the areas of chemical biology that truly absolutely has to be interdisciplinary. It requires a solid understanding of the logic of organic chemistry and a working understanding of how biological systems work to do. It absolutely has to be that way, and there's no interdisciplinary for the sake of being interdisciplinary and capitalizing on chemistry-biology interface grants and nanogoldparticleconjugatedtocrapplusaclickreaction in cells. There are many many ways to approach these questions from synthesis to crystallography to genomics to isotope labeled feeding experiments to mass spec and on and on and on...endless applications of areas of chemistry that I like in their own right.

So anyway, I'm sick of defending myself on this front. I've been exploring various fields of chemistry and biology and working in different types of labs since I was 18 years old. I've wandered around in my coursework. And now I think I've finally settled on something that's right for me.

This is dumb

2009-10-30T20:59:00.000-07:00

I was reading a paper today, and it indicated in its figure legend that it used CS ChemOffice to draw some organic structures. And I begin to wonder, why the fuck is this information necessary to include in a figure heading?

I mean, I get with proteins and shit that it's important to say what program you used for your refinements and such when presenting a structure because...uh...that's part of your method. But this a) was not presenting novel results--just giving background in the intro and b) is there really any substantial difference between a line drawing made in ChemDraw versus a line drawing made in IsisDraw/BKDraw/ChemSketch/whatever? Why don't we say "I did my word processing in Microsoft Word." Or "I analyzed my data in Microsoft Excel." "I did my lit searches in PubMed." Or "I looked up this reaction on SciFinder". Or "I edited my gel images in Adobe Photoshop". Yeah, I guess you get the picture. I just don't understand why this is in a JBC article.

Step I in applying to graduate school

2009-10-20T17:31:00.001-07:00

Took the general GRE today and took the subject GRE a week ago. The general didn't go as well as I hoped, but at least they show that I'm not totally retarded.

This means I'm done with standardized tests forever?

Switching gears...

2009-08-30T23:13:00.000-07:00

I spent time today scanning NCBI for start and stop codons and got an email from my advisor about how we would discuss whether I should put my protein in a GFP or SUMO plasmid and what restriction sites would work tomorrow. I really am going into biochem land.

thesis

2009-08-28T00:21:00.000-07:00

So I've got a thesis topic for my undergrad thesis. And a thesis meeting early tomorrow morning with my two advisors. I'm pretty psyched about it. I'm going to be co-advised by one of my favorite profs at Reed and someone who works in the area of natural product biosynthesis at Portland State University.

The project is going to be to clone and express two enzymes responsible for an interesting transformation in an antibiotic biosynthetic pathway. If I manage to get them pure I'm going to assay them with the appropriate analogs of the natural product and attempt to characterize them. One of them is interesting because it shows no sequence homology to the class of enzymes you would expect it to be in. It's required for the biosynthesis in knockout studies at the genetic level, though so it will be interesting to see what the deal is there (if I get that far).

So basically messing around with cloning and expression for nine months. Protein biochemistry is my one big gap right now in my lab training. I've got basic molecular DNA & RNA techniques down, I've done some cell bio stuff like ELISAs and Westerns and histology and various biochemical assays and shit, and I know how to do synthetic organic chemistry. But I haven't worked with cloning and expression and protein purification and all that stuff that makes you a real biochemist.

I hear protein work is boring as shit and frustrating as hell. But running silica columns is also boring as shit and can be frustrating as hell. So I guess I will finally have a true opinion of which is more boring: cloning or silica columns. And I can tell my chemist and biologist friends to STFU because I know all of boring, thank you very much, in all of its flavors.

Anyway, my general philosophy on this matter is that all fields of science has its boring and you just choose your boring and go with it. I can get through boring--the project just needs to be interesting. To quote the aforementioned Reed professor "Experiments suck. Until they don't."

lab notebooks

2009-08-14T16:15:00.000-07:00

So here's something I've been thinking a lot about lately: lab notebooks.

Lab notebooks are something that I have a bit of a love/hate relationship with. I understand the value of a good lab notebook, and I try to write down everything that I do in it. I also find updating my lab notebook to be a rather tedious and annoying process. For the most part, my lab notebooks are reasonable, but the more complicated a project is and the more techniques I use, the more difficult I find keeping an accurate record to be, and my last lab notebook from this summer, while it contains everything that I did in it could be...uh...slightly better organized. When I was working on a project that was just organic synthesis, it was much easier to keep a good lab notebook.

But I guess, the strangest thing to me about lab notebooks is the fact that when you're done with a project, it stays in the lab with your boss. Of course it does; it's not your property. The record needs to be kept in case someone else needs to follow it. But it is a little strange to have something that's recorded in your handwriting, in your style, in a way that is comprehensible to you just gone, in someone else's hands forever. It's like parting with my diary, my record of my life for the past two months. It's strange.

Fuckity fuck fuck fuck

2009-08-11T09:54:00.000-07:00

So I'm doing this experiment where I'm trying to get a bioengineered polyketide pathway to incorporate weird starter units. I did a small scale feeding experiment and got a promising looking result in terms of retention time, MS-2, and UV spectra. So then I did a 20L fermentation with hopes of eventually isolating it and getting an NMR.

First I did a huge ass silica column to get a crude seperation of the ethyl acetate extract. Then I did a huge ass sephedex column to get a better seperation. Then I did preparative HPLC to get 2.6 mg of something. I took a proton NMR. It was garbage. There were just too many compounds with similar retention times in there to seperate it, and the proton NMR was entirely too dirty to be at all informative. Basically, I couldn't see a lot of the diagnostic peaks at all, and a bit disheartening. BUT! It could have been that it was just too dirty. So on to further purification!

So then I purified my 2.6 mg on the analytical scale HPLC that has a really intensely good column with really great seperation. I fussed with the method with my supervisor for several runs and eventually got 2 peaks that had UV spectras consistent with my compound of interest (with this really fancy-pants analytical column, there were about nine peaks that showed up as one peak on the LC-MS spectra and maybe 4-5 peaks on the prep HPLC column, it was intense). I collected both peaks and started to evaporate them down on the rotovap using a vial adaptor that you can attach to the bump trap. One of my fractions was fine--I can put it on the vaccuum pump overnight, see if there's enough compound for an NMR (for the 500 MHz, you can get away with a little under a mg and still get spectra, so maybe if I isolate 0.7-0.8 mg of it I have a hope of doing the whole proton, 13C, COSY, HMBC, HMQC, etc. thing to really confirm the structure) and if not at least LC-MS it to see if it is there. There are more fractions from the spephedex column that one could purify--ones that actually had better seperation than the one I did attempt to purify (long story involving leaving in less than a week and the time it takes to get LC-MS samples and access to the prep HPLC in a large lab where a lot of people need the equipment)--but I simply don't have time to do it.

But the other fraction...well, what happened was a disaster. The vial adaptor LEAKED AND THE WHOLE VIAL AND BUMP TRAP FILLED WITH WATER FROM THE ROTOVAP BATH! FML!

So now I rinsed the vial and bump trap with MeOH, and am re-evaporating it and putting it on the freeze dryer overnight, hoping to god that a) something comes out, goddamn it, and b) it's not my compound of interest anyway (it was the less promising of the two peaks..but who really knows).

Seriously, though. FML.

2009-08-09T14:22:00.000-07:00

I am going to have an honest appraisal of my scientific strengths and weaknesses. Let’s start with the negative:

I have trouble with school. I’m not an abysmal student, but I’m not an exceptional one either. I have trouble with exams, and you’ve probably seen this whine before. For whatever reason, I have difficulty presenting information on a page that is demonstrative of my conceptual understanding of material—and all of my professors have commented on this. My current boss, actually, who is a brilliant PI, claims to have had similar problems as a student. He is extremely creative, has an encyclopedic knowledge of his field, is able to pull the right people together to manage a productive lab dynamic, is able to follow over 30 people’s projects (many of whom have multiple projects), and is able to publish in great journals in part due to his great sense of presentation and his ability to spin results into narrative stories. He tells us that he wanted to study biochemistry in university but his grades were too bad so he had to study chemistry instead (he’s German, so there you have to choose your field of study before you start), and that for whatever reason he just didn’t fit in the mold that school expects from you. My professors keep telling me that this will really only be a problem that will persist through my first two years of graduate school, and that it’s unfortunate, but wouldn’t it be worse if it were the opposite—I flew through my coursework and then I crashed and burned in a research project? I suppose that’s true, but it also makes getting into a decent program more of a crapshoot.
I’m a little bit messy and spacey and I have difficulty with attention to detail. I’m just not a meticulous person by nature, and I tend to do spacey shit like letting something go on the rotovap for ten minutes before I realize that I forgot to shut the vacuum every now and then. In written work, I have difficulty with catching typos and small but stupid chemical errors like dropped carbons. Usually, at least in lab, when it’s really important I can focus, but sometimes…sometimes shit happens.
I have a really shitty math background. Math has never been my strong suite, and I’m in a program that let me get away with taking very little math due to the way math is taught at our school (i.e. for mathematics students, we don’t have applied math classes for science students since it’s not the liberal arts “way”). Of course, I needed to get through physics and physical chemistry, which means I have some basic competence with algebra and calculus, but I imagine that if I ever need to take stat mech or biophysics or biophysical chemistry or anything like that in grad school, it’s going to be a fight. I just tend to look at scientific concepts in more pictorial terms.
Adding to the "messy and inattentive to details" bit, at times I will cut corners that I maybe shouldn't cut when I'm under a time crunch. My lab notebook, for example, gets progressively worse the more I work on a project. Again, I think this is normal.
I really can't handle extremely aggressive people. A lot of the cutthroat competitive behavior I find pretty distasteful and I'm generally pretty intolerant of that kind of BS. It strikes me that there are a lot of these type of people in science--especially science at a high level--and I need to learn how to deal with them.

Okay, the positive:

I’m always praised on my creativity and the degree of sophistication that I have in putting together scientific concepts, and this has come from professors, my current boss, and the PhD students that I work with currently.
I’m always praised on my ability to process the concepts and link them up to what I am physically doing in lab. One of my supervisors told me that I have such a high understanding of the theory that it’s often difficult for her to remember how much help I need with the little lab things that only come with experience, one example being how much trouble I had figuring out the right way to set up my first sephedex column. I had done many silica columns, but there are a few tricks that you need to do with sephedex columns that I just didn’t know. But she says that there are many undergraduates who come in and they don’t really have the big picture of what they are doing and why they are doing it.
I’m very good at processing the literature. I know how to find papers and how to mine them for information. I also can competently read organic chemistry (synthetic, mechanistic, and natural products), biochemistry, and molecular biology papers. I’ve also been told that I know how to write about/talk about/communicate science in a story after reading papers/seeing talks/working on a project. At least profs tell me positive things when I turn in term papers.
Sort of combining all of the above points together, I noticed that people tend to give me more autonomy in lab after I chat with them about science a bit. This is kind of strange, because just because I have the conceptual framework in my head doesn’t mean I need any less help getting the wet work to work. But I think there’s a psychological component with people where they are more likely to treat you like a colleague when your ideas are in place. That comment isn’t meant to under-value good lab skills, though.
I have the obsessive sort of personality that once I get started on a project, I get completely and totally into it and don’t want to stop. I can be a bit of an obsessive work-a-holic from time to time. It’s difficult for me to disengage and I’m either completely into it or not into it at all. I suppose this is a good quality to have as a research scientist.
I really like working with my hands in lab. Doing office work all the time is boring, and I think physically doing things with ones hands is sort of relaxing (sometimes; unless it's annoying).
I have a good intuition for organic chemistry and bioorganic chemistry in terms of structure and reactivity. I just sort of know what reactions are reasonable, what structures are unstable, and have a solid sense of this in my head.
I’m pretty good at spectroscopy, especially NMR. I’ve got a lot of chemical shifts, j-values, and solvent peaks for proton and carbon (well not j-values, but whatevs) in my head from doing a lot of synthetic organic chemistry, and correlations make sense to me. It’s the sort of visual puzzle that I’m good at, and I have a fair bit of experience with it. I’m also decent with MS, UV, and IR.
I’ve got a decent knowledge base in a variety of fields. Along with knowing organic chemistry, I also know a fair amount of biochemistry and molecular biology, both the theory and the lab techniques. I’m kind of one of those hybrid interdisciplinary scientists, and this is just because I really do like it all.
I'm pretty used to the idea that shit doesn't work most of the time in science. I guess I've spent enough time in labs to figure that out. Having shit not work doesn't really bother me that much--you just need to keep trying and hope that with hard work and a bit of luck it will all work out.
It's pretty drilled into me to write everything in my lab notebook and label everything. One of my profs said that it was very easy to repeat reactions that I did and to keep up the good work. But my synthetic organic lab notebooks are a lot better than, say, the project I'm doing now where I'm never sure how much to include and there's a lot of "continued on page XXX" and MS spectra after MS spectra. My molecular biology lab notebooks are the worst, especially when I'm using a lot of kits.

AA structures

2009-08-02T06:28:00.000-07:00

I recall last year a senior biochem major told me that she had forgotten the structure of the amino acids over the summer DESPITE THE FACT THAT SHE WAS DOING A THESIS ON PROTEIN BIOCHEMISTRY*. This horrified me. She was a great student, a hard worker, got good grades, etc. I guess people give memorizing structures a bad rep, but I think if you get a degree in biochemistry, you should fucking have the amino acid structures in your head, IMHO.

So today, I decided to test myself to see if I was being too judgmental. I needed to memorize the structures of the amino acids and the one letter codes last fall for structural biochem as well as the nitrogenous bases, so it's been several months since someone demanded that I have this knowledge at my fingertips. I guess took another biochemistry course after that, and I look at a lot of nat. product structures, so it's not like I just shut my brain off to biochem and peptides since I took that course. So I drew them all out from memory today just to test myself.

And I knew all of them still. All 20 of them right, suckers! Well, the one letter code for aspartate slipped my mind briefly, which is D, by the way. And I stupidly dropped a hydrogen drawing a couple of the bases. But I still knew which places had carbonyls and which had amine functionalities.

So phew. I guess I still feel justified in calling myself a biochemist, and in holding people to this standard. Is this an unreasonable standard? I dunno. I don't think so.

*okay, it was enzyme kinetics, so she wasn't exactly looking at her protein structures all the time--just dealing with bi-bi ping pong shit, but still. Still. Degree in biochemistry.

angst

2009-07-27T12:31:00.000-07:00

I'm starting my last year of college in the fall, and this is causing me more mental angst that it probably should. It stems from feeling unprepared for dealing with What Comes Next.

Senior year at Reed is a pretty hyped process. Everyone needs to write a senior thesis and the science seniors lock themselves in the lab and look haggard and depressed by shit not working and start prematurely behaving like grad students. They keep odd hours and are totally devoted to their thesis at the exclusion of everything else and thus whine-a-thon culture is encouraged by the culture of the school. At the end you need to give an oral defense and (in the chemistry department) an oral presentation to your classmates during one of the seminar days.

I have a lot of plans for next year, perhaps too many. I got in contact with a professor at a neighboring institution who works on polyketide biosynthesis so I can continue work in the area that I'm doing this summer because it fascinates me. I'm excited, but I have no idea what to expect and whether I've cut out more work than is strictly necessary in facilitating this project that involves a Reed advisor and an advisor from this neighboring institution. Hopefully I'll manage to arrange a project where I can have a Reed lab setup for instead of having to commute to the neighboring instution to do my labwork (I don't have a car) so that I don't loose time constantly, although I'm worried that our instrumentation is not adequate.

I'm also tentatively trying to organize a journal club starting in the fall, and trying to organize an independent study project in the spring on biomimetic synthesis. My rationale for the independent study (not a lab independent study, but a reading papers and writing a review-style document at the end sort of independent study) is that it's more interesting to me than taking a structured course and probably just as much work. I don't really like taking exams much, and I read papers all the time anyway, and it's in a subject that's not really related to what I'm probably going to do my thesis in (thus a bit of a mental break from that), but in a subject that I have a lot of interest in. But I suppose I might feel differently about it at the end of next year.

And I'm trying to figure out this whole grad school shit, while angsting about it and paging through professors' webpages and sending emails instead of hammering through GRE problems. I mean, I've little bit of GRE prep, but not a sufficient amount, and as the days crawl closer and closer to the academic school year, this is starting to stress me out more and more. The problem being, I guess, that I'm pretty caught up in my labwork here. Studying for standardized tests is boring, whereas labwork and paper reading is engaging. I fear this problem will be the exact same one I'll face in the fall. I also have to take a stupid analytical chemistry course that I know I'm going to abhor that will probably get pushed to the last priority.

Meticulous vs. Messy chemists

2009-07-27T11:28:00.000-07:00

I have come to the conclusion that there are two archetypal "types" of organic chemists.

The first describes my labmate last year and one of my current labmates. This is the anal retentive, obsessive compulsive, neat, constantly tinkering, "hood is spotless" chemist. These chemists have a hugely obessive attention to detail, love excel sheets (one has an excel sheet with the CAS number, boiling point, density, and molecular weight of every compound he has dealt with ever, organized by type--solvent, catalyst, etc.), cannot stand if someone gets a drop of anything on the vacuum pump, never have sodium sulfate or silica crust on the surface of their hood, and are crazy-intense. Some people need this to be productive.

The second type of chemist--which I fall into--is the messy chemist. These chemists know when it's important to be meticulous (like when a reaction really needs to be totally anhydrous to work and will be very careful to work dry in those situations), but are okay with being sloppy from time to time when it really doesn't matter. Their hoods might have some dirty glassware awaiting cleaning, probably because they started another reaction before getting a chance to clean up. The surface of the hood might have a bit of silica gel crust from hastily pouring a column (but when it comes to actually running the column, they are very precise). Their organizational system makes total sense to them, but perhaps from the outside might seem bit in dissarray. They realize that it really doesn't matter whether you work something up with 30 mL of the aqueus layer or 50 mL. It just simply doesn't. The messy chemist, while inattentive to some details, is probably obessive about others, like, say, labelling so that they can keep track of everything they are doing at once. And they probably have some bizarre OCD system, like the way they have their reagents arranged on the bench and when it's disrupted they're like WTF DID YOU FUCKING DO TO MY FUCKING CHEMICAL SHELF? And people are like "dude, you're shit is everywhere, and you are about something little like someone putting one bottle in the wrong order? you are a MASSIVE hypocrite."

I think both chemists types of chemists have their merits and drawbacks. For example, while being meticulous is generally praised in science, a lot of the meticulous chemists really can't multitask at all because they are so busy tinkering and making everything just so which can lead to them being less productive overall. On the other hand, some of the messy chemists tend every now and then make a wrong call on whether meticulousness really matters or not. All in all, there's a place for both types and both types can be very good chemists, but it can make lab dynamics a little rough if messy chemists and meticulous chemists need to share common space.

Boring talks

2009-07-27T11:06:00.000-07:00

So, the lab's summer retreat is coming up. I'm going to be back in the good ol' US of A at the time, but I get to hear about it, and one thing is that everyone needs to give a talk.

These talks can be about whatever anyone wants to talk about, whether it's related to their research or just some random topic they find interesting. For example, last year someone decided to talk about whether science and religion were at odds with one another (this topic is dull, sry, I just am sick of hearing about it), which apparently started a lot of discussion.

Anyway, the PhD student I'm working with is trying to come up with her talk. The other talks that people are giving seem pretty dull so far. This one guy is talking about lab safety and security (snore), this other guy who is one of those obsessively meticulous tinkering organic chemists is talking about how to use lab equipment properly. He basically is going to go on for ten minutes about how no one really knows how to use the high vacuum pump correctly and you actually do it like this and blah blah blah blah blah (the PhD student I'm working with said she hoped she would be drunk by that point). Someone else is talking about the antibacterial problem, bugs versus people, which, while in principle is interesting, it's a topic I've heard so many times that it's become pretty dull. I guess last year there was a talk about how to troubleshoot PCR (change the Tm, change the cycles, change the magnesium chloride concentration, etc. etc. ad nauseum), time management, and teamwork in science.

I suggested that she give a talk on how to multitask in lab. I mean, if someone can talk about how to use lab equipment, then why not? She's famous for being "a scientist on speed" and always running 90 million things in parallel. The other thing I suggested was that she give a talk on the chemistry and health benifits of coffee. She's a huge coffee drinker, so it would be pretty amusing. Then I suggested that the other PhD student I work with should give a talk about how smoking cigarettes lowers your risk for Parkinson's (since he's know for being a chain-smoker). That might cause a few laughs, at least. And the dopamine axis is pretty fascinating.

But anyway, I think I'm going to make a list of boring talk topics that I've had to sit through:
1) How to use Web of Science. Really, seriously, it's a frickin' search engine.
2) How to use Sci-Finder. This was useless to me, because things like Sci-Finder (and Web of Science) are things that I just need to tinker with to really learn how to use.
3) Lab safety in all its iterations.
4) How to properly tutor someone, how to deal with personality clashes, how you weren't supposed to have whine and commiseration sessions about particular professors during tutoring, etc. etc. During that seminar I wanted to ask, just to be obnoxious by the end "what do you do when if you sleep with your tutor/tutee and they won't respond to your emails because shit got awkward?"

So yeah. I think horrendiously dull talks should be outlawed.

lab safety

2009-07-23T11:50:00.000-07:00

There is one PhD student in my lab whose job is to be safety hardass. This means she's constantly yelling at me to wear goggles--something I can never remember to do unless I'm working with something that will light on fire if it's exposed to air or if the pressurized air is being really strange and popping the top off my column and it's freaking me out. The thing is, most days I wear very large-framed hipster nerd glasses anyway and as far as I can tell, they protect my eyes just as well as any of the lab glasses--perhaps better than the ones that don't look freakishly nerdy. In order to find goggles that actually fit over my hipster nerd glasses I need to get the huge ass glasses that fall off my face and are a huge nuisance because I'm always pushing them back up and I really don't like having my gloves that near my face when I'm, uh, working with shit that might be toxic. Furthermore, for 90% of the things I do, I really can't understand what could possibly go wrong. Okay, so maybe I'll get some ethyl acetate in my eye one day. Big fucking deal.

I understand that I'm much more lax about saftey much of the time than is entirely wise, and I'm trying to get better about it. I mean, I'm not hella old school like this one very old PhD chemist research assistant at my school who says "gloves are for pussies" and refuses to run columns containing chloroform under the hood and turns off the hoods when he feels like that lab is getting too cold. That type of shit freaks me the fuck out, and I rather like fume hoods because I dislike feeling woozy. When I TA sophomore organic lab I'm always yelling at people to keep chemicals under the hood because when 20 people are keeping beakers of ether on the bench it makes me feel quite ill. But occasionally I'll forget to wear gloves when I really shouldn't and I've spilled far more chlorinated solvents on my hands than is probably ideal. I also work with natural products quite a bit, and while my streptomyces aren't pathogenic and the compounds I'm trying to isolate are not accutely toxic as far as we know, you never know for sure, I really should always do those extractions with gloves. OOPS. It's all pretty dilute, but still. There are some people in the lab who work with very very toxic natural products and they need to be hella careful. But I'm also 21 and in that phase where I don't really understand the long-term consequences of my actions at all and feel like death is far and I am immortal. And as far as I can tell, a little bit of methylene chloride stinging my hands every now and then, while unpleasant, is not going to kill me. The other thing is, I've gotten into the biologist mode of thinking that being careful is not to protect my health, but rather it's to protect my experiments from getting fucked up, like working sterilely and shit.

But anyway, I digress. Today I was cleaning up after a prep HPLC I did on Tuesday of a synthetic compound I made recently. After finishing evaporating down fractions and making up an NMR spectra and such I needed to dispose of the rest of my fractions. I came in, asking where the waste for re-distilling acetonitrile went. I touched the top of my test tubes from my fractions (not, did not get liquid on myself, just touched the upper rim, where anything that was ever there would have evaporated off anyway). Immediately, this PhD student yells at me "DON'T TOUCH THAT IT MIGHT BE TOXIC!!!!"

This took me aback for a second because, well, it was said in an exceedingly aggressive tone. And even thought I'm just a baby undergrad, I really dislike when people condescend to me. It's one thing if you're like "hey dude, it would be a really good idea to wear gloves while you're working with that, because, you know, DCC is pretty toxic or whatever," but this was different. The thing that seemed really illogical to me was that the fractions I had were almost entirely acetonitrile and water. My compound was not in those fractions, and the only toxic things that may have been there was trace amounts of DCC (which was primarily removed in the workup anyway) and other side product junk that might have been present in very trace amounts. And my compound was not exceptionally toxic either. I mean, I certainly wouldn't eat it, but it's not something that would make me pass out if I spilled less than a miligram of it on my hand. Ironically enough, the student who was yelling at me was a smoker, which is far more carcinogenic than trace amounts of standard synthetic materials getting on your hands as far as I know.

And so, yeah, the explanation I get for such aggressive lab-saftey seriousness is that the lab is liable for anything that occurs there. But the lab is not responsible for a stochaistic effect that may happen 30 years from now for reasons that are entirely untraceable to one day of carelessness in discarding some prep HPLC samples. So I wish people would chill the fuck out about shit like that. It's my body to abuse as I choose.

I guess I just don't understand. For example, in the chemistry lab I handle carbiimides all the time on the normal scale weighing them out, which are pretty frickin' toxic. Yet when I'm visualizing a gel, there is a lot of paranoia about getting ethidium bromide anywhere. Like, special hoods and you can't bring plastic epi-holders from the EtBr hood to the rest of the lab. It just seems to me that the way lab safety is handled generally is completely absurd, and while it is definitely important, it's also not worth flipping out about to the degree that most people do.

Unless you're working with something that is seriously accutely toxic. Then it's well deserved. But if you treat everything like you're going to die if you touch it, it kind of undermines how careful you need to be with some things, I think.

Biomimetic synthesis

2009-07-22T13:47:00.000-07:00

Lately I've been getting really into biomimetic synthesis.

It's interesting to me because one criticism I hear a lot of total synthesis is that it doesn't ask questions. Or rather, the question is, "can we make this huge-ass natural product with eight bajillion stereocenters?" and the answer seems to always be "with enough depressed, overworked graduate students, yes?" It's been described to me as the "climbing the mountain" metaphor by a professor, whatever that means. Actually, it's mostly molecular biologists, I've noticed who go on this Theory of Science rant about the scientific method (observation, question, hypothesis, experiment, knowledge or some variant of that) and how synthetic organic chemistry doesn't follow it. It's a favorite rant of a physiology professor of mine's.

Then, as far as I can tell a lot of mechanistic organic papers are like "so dude, we noticed this stereochemistry forming and thought that was cool so we invoked a Hatree-Fock 31-G transition state model and then examined some MO secondary orbital effects and tried to rationalize the stereochemistry and found out that this other cool reaction also occurs so we examined that too and it occured in an x:x dr because of blah (probably)". I had a physical organic chemistry class where the professor was really into asking us questions like "is this paper hypothesis-driven or a data-driven?" and then he and I would get into long discussions in his office/email exchanges afterwards about it because I nearly always would claim that the paper read like a fishing expedition. But I digress.

Biomimetic synthesis is definitely hypothesis-driven, because it asks the question, "is this putative biosynthetic pathway plausible?". Furthermore, the stereoselectivity lends evidence as to whether the reaction is enzyme-mediated or spontaneous. If the natural product is racemic, it's probably spontaneous, but if it's enantioselective, it's probably not (but, as one person pointed out in a paper I read recently, the cell is a chiral environment, so perhaps that is leading to some stereoselective effects that are difficult to predict) . I read of this one example of a biosynthetic Diels-Alder reaction that only resulted in the exo product, despite the endo product being highly favored in the RBF. Or, if you can only get stereoselectivity with a Lewis acid, that indicates that there is probably an enzyme there performing the role of the Lewis acid. And this is really cool, because you can think like a synthetic chemist, but you can also ask questions about how the world works. And not just at an abstract theoretical MO level, but at something that's a little more discrete to me--a biosynthetic pathway leading to a metabolite structure.

I guess it's also appealing to me because I finally have enough of a background in pericyclic reactions (due to the aformentioned professor and the aformentioned physical organic class, which was called "Advanced Mechanistic Organic Chemistry") to make sense of all these 8π-6π electrocyclization cascades and Diels-Alder reaction selectivity nuances and Cope rearrangements and [1.7] hydride shifts. And some of the structural rearrangements are wicked. They are generally basically just pericyclic refoldings of polyenes derived from fatty acids or polyketides. It blows my mind that something so simple can re-arrange into such a vast structural diversity.

The other thing that occurred to me while reading these papers, is I recall (sorry, I'm too lazy for refs at the moment, although I really should link most of these papers) that in the past few years there have been several papers on "On Water" Diels-Alder reactions. Sharpless has done a bunch of work on this, and the principle is the same principle that drives most of structural biochemistry in terms of lipid structure and protein folding: the hydrophobic effect and solvent entropy. There have been some pretty impressive rate and stereoselectivity enhancements from doing Diels-Alder reactions on water, since the reagents are forced to be in close proximity, minimizing the entropy of finding one another in a reactive conformation relative to being dispersed in solution. Since many Diels-Alder (and other pericyclic) reactions require thermal conditions that are far from physiological (beyond weird thermophilic archea and such), it's interesting that there is such a rate enhancement from these on-water reactions, and I imagine that there's a lot of work in the future that needs to be done to elucidate exactly how the role of the cellular aqueus environment impacts the kinetics of these biosynthetic reactions.

On Review-Writing

2009-07-22T12:51:00.001-07:00

About a month ago, my PI asked me if I'd like to write a minireview with him. This was like "whoa seriously?", and I dove into a huge pile of papers on primarily pretty obscure natural products research. This is really only an opportunity afforded to me because a) my PI is a really nice guy and b) I'm an American abroad, so being a native English speaker is considered a huge advantage and c) I have no idea, it just sort of happened when I was in his office one day. I've been slogging through a ton random plant pathways in old articles from the '70s and '80s in Phytochemistry and huge exhaustive Angewantde reviews on polyketide biosynthesis and biosynthetic Diels-Alder reactions and Natural Products Reports reviews on biomimetic synthesis and so on and so forth.

I'm kind of known in my lab for being strangely obsessed with reading papers for a 21 year old student who isn't done with her bachelors yet. I don't know when I got into this habit, I guess over the past year or so I realized that reading papers on my Google Reader RSS feeds was a great way to procrastinate memorizing point groups and doing arduously long problems on the Boltzman Speed distribution when I just wasn't in the mood for it. It's also a habit, I guess, that people encourage in me, like attending seminars, so it tends to get reinforced. I am lucky enough to attend an undergraduate institution that puts a lot of emphasis on processing the primiary literature, so in a sense doing a minireview is just a step up from writing a review-style term paper, which I have written several of. It needs to be more polished and incorperate more references, but in essence the task is the same: read a shitfuckton of papers, summarize them, re-draw a bunch of schemes in ChemDraw the way you want them drawn to illustrate your point, and keep reworking the document until you're like "when the fuck will this goddamn thing be written?" while somehow perversely enjoying the process.

So, I have a first draft written, and thus I've stepped into the process of starting to seriously write it instead of it just being some abstract Thing. It's just I talked to my PI last week and he was like "oh yeah, well I think we should re-order the examples like this and this and this and by the way this random metabolite pathway actually incorperates this intermediate not the one you have drawn and here's 8 million more references because I think you should talk about xyz pathways as well. But I don't want it to be exhaustive! Oh, also, you should download the paper template to the journal I want to submit it to, even though we are far from done writing it." I'm a little bit overwhelmed by the prospect of re-ordering all the ideas and putting them in a cohensive whole because, well, god, I don't know, it just really is a lot of work that still needs to be done. Also, I fucking hate when you track down eight references from some obscure research done in the '80s only to find that there was a relatively recent review article that incorporates much more recent findings on the topic that for whatever reason just wouldn't show up in your original Web of Science search. You find out in review writing that there's a lot of trash published in the literature, like structures that are just plain wrong or have ambiguous stereochemistry when they really shouldn't (endo or exo isomers in Diels-Alder reactions are, uh, kind of important, and you'd think something that one could elucidate via NMR) and a lot of citations that are just wrong (like papers that were published in 1982 cited as being published in 1992? and when you can't track down the reference you're like...wtf is wrong with me? oh wait. no, it's not me, it's them). I guess I also have my fair share of problems with making stupid chemical errors in my schemes and reference list, though, so I shouldn't be so harsh.

Also, I seem to have some paper that for the life of me I can't figure out what it has to do with the topic I'm writing about. I'm pretty sure it's a paper he handed me and not one I found on my own. It's like "blah blah blah his tag blah blah blah PCR blah blah blah protein expression blah blah blah enzyme blah blah blah iron center blah blah blah".

But yeah, it's a process. An interesting one, at the very least.

2009-07-18T13:37:00.000-07:00

Everyone in my lab thinks that I'm a chemist by training. My degree is going to be in "biochemistry & molecular biology," but they all think I'm a chemist because, beyond a little bit of microbiology, I mostly do extractions, a little bit of synthesis, and a lot of staring at MS and NMR spectra. This is strange to me, because the synthesis I'm doing is basically a simple coupling reaction. It's a one-step synthesis to make substrates for my bacteria. Although purifying the shit on a column is always a bit of a pain (I fucking hate silica gel columns even though I do them basically every other day now), it's pretty much chemistry that anyone with a little bit of lab experience and someone to show them how to use the argon-line should be able to do. I mean I know how to set up organic reactions, work them up, purify them, and analyze them. I can follow a lit prep, but that doesn't seem so special to me. I'll be the first to admit that I'm more of a chemical biochemist than a biological biochemist, but I'm also pretty early in my training.

I guess in a sense I'm a bit of a weird biochemist in that I'm exceptionally interested in organic chemistry. I've done some organic synthesis research, and I guess I know about as much organic chemistry as any undergraduate interested in organic chemistry could be expected to know, but much much less than anyone who really calls themselves an organic chemist. I can make it through total synthesis, methodology, and mechanistic papers as long as I do a little bit of wikipedia-ing, I have a basic set of background knowledge of useful synthetic reactions, and I'm pretty decent at interpreting proton and carbon NMR spectra. But this doesn't mean anything. My undergraduate synthetic projects were trivial relative to what real synthetic chemists do. Christ, my synthetic target on my last project didn't even have any non-trivial stereocenters. And anyway, I also know how to do enzyme assays and Western blots and PCR and reverse-transcription and all that shit. It just doesn't happen to be what I'm doing for this particular project.

To me the borders of biology and chemistry are entirely trivial and artificial anyway, and being expected to regurgitate the derivation of the Boltzman distribution on an exam (which was required of me for my biochemistry degree) is far more "different" to me from protein biochemistry and molecular biology than being able to run a fucking silica gel column. I'm just not sure why it's so strange to everyone that I'm a biochemist by training who is also has decent organic chemistry lab hands. Yeah, okay, you transfer small volumes in molecular biology and large volumes in chemistry, but in a sense it's all the same. Transferring liquid, following preps, troubleshooting.

It's especially strange because it's a very interdisciplinary lab where everyone needs to do a little bit of everything. I mean, even if you're a biologist, you've probably seen an NMR spectra and even if you're a chemist you've probably done some bacterial culture in my current lab. Yeah, everyone is a specialist in something or another, but everyone also needs to be reasonably literate in fields outside of their own because the nature of the projects are so interdisciplinary and collaborative.

When it comes down to it, I think what's most telling about the fact that I'm not really a synthetic organic chemist is the fact that I consider synthesis to be one more lab tool to use investigate interesting questions rather than the intrinsic puzzle of making a complicated structure. To me, methods are methods. They are important, and it's important to learn how to do them well and how they work. But at this point in my training, there is always someone (a professor, PhD student, or post-doc) to teach me the methods. So whether the methods are chemical or biological makes no difference, really since I'm just at a stage where I'm learning how to think and troubleshoot anyway.

But damn, do people like their catagories. This is something I'm going to have to learn to deal with if I want to stay in interdisciplinary science.

On Being an Undergrad...

2009-07-18T13:32:00.000-07:00

The annoying thing about being a wee-little undergraduate student is that at my current lab, for safety regulation reasons, I’m not allowed to do labwork “unsupervised”. This means that someone has to be in the wing I’m working in while I’m working. This is understandable because I don’t have a degree and I might fuck shit up I guess, but on the other hand it’s really annoying. When I’m in lab, I’m rarely “supervised” in that it’s very unusual that someone is sitting with me looking over my shoulder telling me what to do. Usually a PhD student teaches me how to do a technique once and then expects me to do it on my own the next time, which is exactly how I like to work. If I’m doing something new or tricky, I might be supervised, but generally I’m off doing my thing and my supervising PhD student is off doing their thing and if something goes wrong or I need help or whatever I might find them but otherwise we’re both on our own, doing our things.

The project I’m working on now involves feeding bioengineered bacteria shit and hoping that they make interesting secondary metabolites with it. Feeding bacteria cultures 5 mg of some strange chemical is not difficult and takes about 15 minutes to do, but since bacteria are living things, the experiment is time sensitive and not always on my schedule. This means that I often have to go in on the weekend. This means that I need to coordinate my schedule with my supervising PhD student on the weekend while she has her life shit going on and I have mine. Which is ANNOYING.

I’m also used to going to a small liberal arts school that is undergrad only, so I’m used to having an exceptional amount of autonomy in lab. When I’m doing lab work I either have a key or swipe card access to the lab, and unless I’m doing something really dangerous or using expensive, tricky equipment that is easy to fuck up, no one gives a fuck whether I’m doing it during the day or at 2 am. I’ve come in hungover on Saturday morning to work up a reaction. I’ve come in at midnight on Saturday to run a PCR. I’ve wandered in at one in the morning to follow a reaction by TLC. In fact, I can think of two things that I’m not allowed to do by myself in lab: use the catalytic hydrogenator (in case it explodes) or use n-butyl lithium (in case I light shit on fire). A couple of my friends procrastinated their lab work so much that they pulled an all-nighter to run a bunch of Western blots and one of their girlfriends called them up panicked because it was six in the morning and they still hadn’t gone home.

So, sigh. I suppose soon enough I’ll have my degree and my own lab space and it will be the time when no one gives a fuck when I’m in lab. But for now I’m a young’un hopelessly reliant on everyone else.

2009-07-14T13:16:00.001-07:00

Among the many things I admire about my boss includes his sense of scientific presentation and his creativity in communicating science. His papers read like narrative stories, and he has a great sense for the right sort of catchphrases to use. I want to be able to write that like.

Combinatorial peptide synthesis

2009-07-01T14:05:00.001-07:00

Yesterday we talked about a paper in journal club from Nature Chemical Biology. It was one of those combinatorial peptide synthesis papers--in this case to find a inhibitor of a protein in the clotting cascade (a serine protease that activated a precurser of a signalling cascade, I guess). It struck me that all these papers are the same. Do some combinatorial peptide (or peptide analog, or chemical altered peptide with some functional group sidechain), create a library of compounds, screen them, and try to find some compound that is an inhibitor or probe or whatever of some protein of pharmacological or biotechnological relevance. The targets change, the screening methods change, sometimes the synthetic methods change (although it's usually some variant of solid phase peptide synthesis). But the general idea stays the same: boring. There wasn't even any interesting structural biology about how the compounds worked as an inhibitor (my PI suggested that perhaps one of the moeities on a segment of the peptide blocked the catalytic triad--now that sort of hypothesis is something I can actually get into).

I guess I wouldn't be so judgmental about this research if it didn't seem like every issue of Nature Chemical Biology (or ACS Chemical Biology or Chemistry & Biology or ChemBioChem or what have you) had at least one article like this. In the introduction they always introduce their methodology as a novel (novel!?!) modular combinatorial method that is very promising as a way to find compounds of medicinal interest blah blah blah.

There's nothing that is really all that intellectually satisfying about this area of chemical biology to me. It's all the same. There's no narritive story to it--just hammering.

Various musings

2009-06-20T06:28:00.000-07:00

The lab I’m in currently is very interdisciplinary. The department is “biomolecular chemistry”, and the PI is originally a chemist by training, but now works with polyketide biosynthesis. His group has biologists, chemists, and biochemists working together. It’s great because there are people with all sorts of specialties, and the biologists have some proficiency in reading NMR spectra, the chemists might do a bit of molecular biology, and everyone works together. When you read his papers, you can tell that he thinks like an organic chemist, and even though he has projects that use molecular biology techniques, the goal of the lab is to understand the chemistry behind biosynthesis.

I’m happy because the project I’ve been working on uses everything I’m interested in: microbiology, molecular biology, synthetic chemistry, and spectroscopy. I’ve done a lot of bacterial culture, a conjugation, a proplast preparation, prepared spore suspensions, extractions, some DNA extraction and a restriction digest, looked at LC-MS spectra, and looked at NMR spectra. I get to hear talks about all these different projects—some chemistry, some biology, some biochemistry. It’s really stimulating because it’s all my interests coming together in one institute.

But what I’ve noticed—even here—is that I get a lot of questions. “Are you a biochemist or a chemist?” Both, I answer—because I really do feel like I’m a little bit of both at the moment. And while there are a couple people that truly are both—one Japanese post-doc for example--most people are one thing or another by training. As I am only an undergrad now, I don’t have expertise-level knowledge in any discipline yet. I’m proficient with basic biology lab techniques and basic (organic) chemistry lab techniques. I know how to read NMR spectra, but I am nowhere near an expert. With an experimental section and someone to show me where things are and how they are done in this lab, I can set up a synthesis and work it up, set up a bacterial culture, or do a DNA extraction. One of my professors described me as “riding the line between biochemistry and organic chemistry” and I guess he’s right.

I’ve spent a lot of time in the past couple years doing organic synthesis, and I consider myself to be proficient in synthetic chemistry (for an undergrad). Yet my degree is in “biochemistry and molecular biology”. I feel like I always have to qualify myself as a chemist by appealing to my prior lab experience and coursework. Yet the biochemists are surprised by how much chemistry I know, and how I talk to chemists. But I’m not just a chemist. I know how to read biology papers. I know how to design primers. I know my amino acids and my DNA binding motifs. I was interested in biology first.

I feel like I’m well on my way to becoming one of those “jack of all trades, master of none” scientists that people seem to disparage so. I read a lot about this on the internet, how these new-fangled chemical biology PhD programs are producing scientists that are neither fish-nor-fowl and know a little bit about everything, but not enough about anything. I hear the “proper” way to go about an interdisciplinary career is to do a classical discipline and diversity from there (i.e. get a PhD in straight up total synthesis, then post-doc in chemical biology/biosynthesis/med chem.) I don’t know why this is seen to be the case. As an undergrad—whether you are a biology major or a chemistry major, you need to learn things that are entirely unrelated to what you will later study. Physical chemistry is entirely different in mindset than organic chemistry; it’s a different language all together. Likewise, a lot of biology programs (such as Reed’s) require you to take evoluntionary biology. While I’m not opposed to this—it’s necessary background—being an undergrad requires you to be very flexible and mutable. You need to learn a lot things that are very different from one another. Why not take advantage of this time—when I’m young and grabbing information, before my mind is set—to really learn about all these things that I’m interested in?

Coming from Reed, which is a very small school, I think so far I have had a rather unconventional biochemistry training. I had the time to take elective chemistry courses, but also there is no distinction between physical chemistry for biochemists and physical chemistry for chemists. My biology classes, likewise, were also biology classes for biologists. The training I have received so far was not so much a biochemistry education (in the classical sense) as both a biology and chemistry education. In fact, it’s probably more chemical than most biochemistry educations, largely due to my interests in chemistry.

The other thing that constantly strikes me as odd is that there seems to be this assumption among biologists and chemists that you can teach a chemist biology, but you can’t teach a biologist chemistry. I think this is absurd, and it’s a notion propagated by lazy biologists and arrogant chemists. I mean, obviously you’re not going to have a PhD-level proficiency in either subject, but I don’t think there’s anything intrinsically more difficult about (especially organic) chemistry than there is about molecular biology. Take two examples: synthetic organic chemistry and cellular biology. Both are incredibly complex, interrelated subjects that require a huge amount of background knowledge. Neither are particularly mathematical, and both are about arranging patterns in your head more than they are about memorization. I really don’t see why a cell biologist couldn’t sit down with an organic chemistry textbook or sci-finder and learn a bit about organic synthesis and more than a synthetic chemist couldn’t sit with a textbook and pub-med and learn about cell biology. It strikes me that there’s a lot of “chemistry-a-phobia” in biologists, and a lot of “my subject is intrinsically harder that your subject” in chemistry that is all a bunch of nonsense.

When can we start calling ourselves an "ist"?

2009-05-21T23:00:00.001-07:00

I was talking to my friend, and I made the mistake of saying "I think I am more of a chemical biologist than a biochemist in the traditional sense."

He said "You're a fricking undergrad. You're neither. What do you mean by that, that you took a few organic chemistry classes and liked them? That's absurd."

Then I said, "You're absolutely right. Right now I am just a student. But what I mean is how I think about science."

He said, "What do you mean, how you think about science, that is ridiculous. I just don't understand what you're talking about when you say shit like that."

But what I mean, I guess, is that in the biology-chemistry interface-land, what is biology and what is chemistry and what is biochemistry and what is chemical biology is totally artificial. But they are words that we use to describe an approach to solving problems, the way experiments are designed, and a school of thought of training.

I mean, one could say "I just don't think like a cell biologist, I think like a geneticist." This means something to me, even though there is a large degree of overlap between what a cell biologist is and what a geneticist is, and a cell biologist better know genetics and a geneticist better know some cell biology. The way papers in Cell are laid out are just different from the papers in Nature Genetics. And not just visually, in the intellectual approach.

Biochemistry is neither biology nor chemistry (although it's both) in a lot of ways. It's kind of its own thing. It's got it's own kinetics. It's got it's own brand of tedious separation chemistry. It's got it's own sort of sensibility. The mindset that I am in when I read a paper from Organic Letters is totally different from the mindset I am in when I read a paper from ACS Biochemistry.

I feel like by junior year, as a student you have a pretty good sense of what sub-specialty of your science training you are good at and interested in pursuing further and what area you are most "minded" like. And as far as I can tell, I'm most "minded" in this relatively new biology-chemistry hybrid business people refer to as chemical biology. Is that so absurd?

Enzyme Kinetics

2009-04-28T11:49:00.000-07:00

I've taken two biochemistry courses now, structural biochem and metabolic biochem. I guess this is a pretty standard undergrad curriculum. Both dealt with enzyme kinetics fairly extensively, and I realized today, sitting in class and going over bi bi multi-substrate mechanisms--ping pong and ordered sequential--that both classes took a totally different approach in allowing us to think about enzyme kinetics.

In structural biochem took an approach where we did Michaelis-Menton, inhibition, etc. but it was always in a "how can we change this interaction in the active site with the substrate to affect catalysis". It was pretty concrete to me, because you can mess with concrete, chemical interactions, like a hydrogen bonding interaction between residues, or some residue that kinks the protein out of alignment conformationally. Km and kcat had a directly linked cause--and that cause was intermolecular interactions.

In metabolic, it's sort of at this gross scale of when the substrate binds and when the substrate comes off. It's taking a step back from structure, and thinking about timing and mechanism at a larger scale. It's no longer this glutamate residue--it's just substrate A binds before substrate B. The mathematics feels so abstract, because I feel like I can't really picture in my head the fact that the blobular enzyme is undergoing small scale intermolecular interactions with the blobular substrate. It's just line drawings; it's schematics. I like it ok, and it's certainly a powerful approach. But what draws me to chemistry is structure, reactivity, and function. It's this viceral visual way of thinking about molecules coming together in space. And that's kind of lacking for me in Lineweaver-Burke plot after Lineweaver-Burke plot.

Incidentally, in reading the enzyme kinetics page on Wikipedia, I found it ammusing that "bi bi ping pong" was a totally technical term, and not a Ron-ism. Ron throws in conventional technical terms (which are, to be fair, often goofy sounding) with his own enzyme kinetics lingo, so sometimes hard to tell what is a general term that the biochemical community uses, and what terms are unique to him and his research. For example, he studies an enzyme that never lets go of its substrate, and so he likes to call those enzymes "Promethian enzymes". If you recall, Promethius in Greek mythology stole fire from Zeus, and to be punished, he had to be chained to a rock for the rest of his eternity while eagles ate out his liver. Then he would re-grow a liver and the cycle would repeat. So I guess that is an apt analogy.

How I'm spending my weekend:

2009-04-25T19:10:00.000-07:00

Pictures tell this story better than words

pKas

2009-04-24T20:07:00.001-07:00

One thing I am apparently good at:

I am a pKa machine. I basically can tell you the pKa of just about any organic molecule off the top of my head. If I don't know it, I can usually extrapolate what it is from related structures and by how well you can stabilize the conjugate base. I continually impress people by this ability and by how rarely I need a pKa table.

Usually I have a shoddy memory for rote memorization, so I have no idea how this stuck so well.

Summer in Germany; Polyketide Biosynthesis

2009-04-24T18:01:00.001-07:00

As I may or may not have posted before, this summer I'm going to do a lab internship in Jena Germany at the Hans Knoll Institute: Leibniz Institute for Natural Products Research and Infection Biology in the department of biomolecular chemistry in Christian Hertweck's group.

The story of how this works is the following: I was writing a paper for my biochemistry seminar which focused on chemical biology and I stumbled upon work he was doing with polyketide biosynthetic enzymes in the aureothin (a Streptomyces thioluteus polyketide) pathway. Specifically, AurH, an enzyme catalyzes the chiral oxidation of a THF ring. This paper caught my attention as a mechanistic paper that dissected how the enzyme worked to act as a catalyst and this paper* used the enzyme in a stereospecific total chemoenzymatic synthesis. I read about how they figured which enzyme did the oxidation using molecular biology methods, along with how they figured out how the enzyme worked with biochemical methods, and then their application synthetically. It intrigued me because it was basically exactly the sort of research I want to be doing. It seamlessly integrates biology and chemistry. It relies on both synthetic organic chemistry and molecular biology. Dissecting mechanistically interesting biosynthetic steps that are difficult to mimic with classical reagents is just a really fascinating area of study to me. So I wrote a review paper for my class about research from his lab.

So one day, kind of on a whim I emailed Christian Hertweck, the PI with my CV. He was impressed with my background and my strong desire to do interdisciplinary science and offered me a summer internship at the HKI. I've been in correspondance all year working out the details. So I will be in Germany this summer doing chemical biology research.

It hasn't really hit me that I will be in Germany this summer doing exactly the sort of science I want to be doing. It seems like such a lucky shot in the dark.

I'm so pumped for this summer and next year. I like learning, so classes are alright, but what I really like is doing research. It reminds me "oh yes, this is why I study science."

Also, this will be my fourth consecutive summer in a lab, along with doing research in my prof's lab during the year for a bit and an undergraduate thesis. Although not my motivation for wanting to be in the lab in the summer, that's gotta look attractive to graduate schools, right?

*As a tangent, I also really like the journal ChemBioChem, which is a European chemical biology journal published by Wiley. ACS Chemical Biology puts out a few interesting articles, but it feels uninspiring a lot of the time (and virtually indistinguishable from what goes into ACS Biochemistry), and Nature Chemical Biology seems differently focused. There is some interesting bioorganic work being done here but the the mentality seems different somehow. It seems like the organic community is more seemlessly integrated in this European journal. More on this later.

Last year of college?

2009-04-16T13:14:00.000-07:00

My course schedule for next year (my last year of college, eek) looks tentatively like this:

First semester:
--Thesis
--Analytical chemistry; graduation requirement. Enough said. I don't think anyone enjoys propagating error and if they do they are a freak of nature.
--Imperial Christianity; religion class, gotta get those liberal arts requirements done, plus it's with a badass prof
--Topics in Biochemistry; a mellow seminar that meets once a week for an hour and a half to discuss papers, next year the topic is the role of metals in biochemistry

Second semester:
--Thesis
--Cellular biology; only going to take the lecture portion of this, though. I've had experience culturing cells and doing Westerns. The only thing I feel like I'm really missing is learning how to use the qPCR machine. In any case I don't want to be in cell bio lab when doing a thesis, but I really would like an introduction to the field beyond what I've picked up over the past few years (i.e. run away from the MAP kinase pathway).
--Advanced inorganic chemistry; it's a half-unit lecture only course. I-chem is just starting to pick up for me since we are doing transition metals and you get to go into the really cool stuff in there; it also derives group theory.
--Intro drama; an English class, I feel like I could use some more literature classes in my life

I have enough credits that I could drop either cell or advanced i-chem second semester and still be good to graduate and may very well do that so I can spend more time on my thesis. More importantly, my classes are clumped together well so that I have a lot of time to spend in the lab.

2009-04-15T19:15:00.000-07:00

Yesterday my boyfriend was sitting in the chemistry lounge, listening to a podcast of an NPR interview with David Foster Wallace. One of my chemistry professors walks by and starts chatting about how David Foster Wallace taught at Pomona at the same time he taught at Pomona.

Alan (my professor): So apparently he wasn't a very happy guy.
My boyfriend: Well, you know, that's what writing about the postmodern condition will do to you.
Me: Or thinking about molecular orbital theory too much.
Alan: Oh that was sharp. Is this a disgruntled chem 324 student I hear? [i.e. advanced mechanistic organic chemistry]

Yes, Alan. Yes it is. I have such a love hate relationship with MO theory. On the one hand it explains...just about everything more or less and is really fundamentally important for understanding chemistry. I switch between thinking the quantum mechanical explanations behind it are fascinating at a conceptual level and not particularly interesting in its details. Bond models feel like bullshit to me; with all the different iterations of orbital theory, I don't know how someone can graduate with a degree in chemistry thinking that it's any more than an amalgam of useful models that sort of kind of approximate reality and happen to explain shit well.

Usually I'm ok with this fact. If I felt that science was free of "woo woo" (as one of my bio profs liked to call things like lit theory and epistimology) then I would really be a headcase. At the same time I'm sick of hearing soc majors after taking a sociology of science class tell me that science is just socially constructed and no more legitimate than any other dicipline of study because, yeah, bonding models do--at some level--contain some "bullshit" but people have still used them to, like, make an LED out of a fucking semiconductor. And band theory is hella useful for explaining that behavior.

Stat therm

2009-04-14T14:49:00.000-07:00

Last night my boyfriend asked me (he's a chemistry major, although a sophomore taking organic right now) what the reagent NBS did. I could answer him immediately and even describe the structure of the molecule and that NBS stood for "n-bromo succinamide".

Organic reagents, pKas, structures of the amino acids, NMR shifts and typical J-values, IR shifts, even some boiling points, this is all at the tip of my fingers. It's just stored in my head--anything organic or bioorganic is just there. I haven't forgotten it.

There's an incredible amount of information pertaining to organic chemistry and biochemistry that is just completely accessible in my head. I do not understand then, why it is so difficult to download thermodynamics equations in there. It's not like I enjoy memorizing pKas anymore than I enjoy memorizing thermodynamic definitions.

I realized earlier today that I have been approaching physical chemistry all wrong. I have a really shitty memory for information without context and so while some people can just cram equations into their head for tests that tends to not work for me. Organic rarely required memorization beyond a few weirdo reagents whose mechanisms were beyond the scope of the class; it was just mastering a few trends and then applying problem solving. Math is like this too, and physical chemistry is math. I need to learn the definitions and work from there and apply problem solving to derive everything I need.

Since I am uncomfortable with math as a language given my poor schooling in calculus, I have generally considered myself not mathematically facile enough to apply this approach to stat therm. I realized today, though, that the memorize special situations equations approach and memorizing derivations approach isn't going to work either, because there is just too much goddamn material for that. And I am facile enough with algebra and calculus...I just need to be confident that is the case. I need to work with the language and do the problem solving.

Why won't the algebra work out?

2009-04-13T23:49:00.001-07:00

Fugacity is currently the bane of my existence.

Electron spin existential crisis

2009-04-12T14:34:00.001-07:00

Last night while studying for an inorganic chemistry exam I have tomorrow, I suddenly had a huge existential crisis about not understanding magnetism.

It went something like this: how does MO theory tell us that oxygen should be paramagnetic and carbon should be diamagnetc?

Well, oxygen has unpaired electrons in its HOMO. Carbon has paired electrons in its HOMO. One or more unpaired electron leads to paramagnetism.

Okay, hold up. So why does oxygen want to have its electrons have the same spin when one goes into each degenerate orbital? Why, well, electrons repulse each other since they are negatively charged, thus if they can, they will go into separate degenerate orbitals (following Hund's rule). Due to the Pauli exclusion principle that means that electrons cannot have the same spin and position. If they have the same spin, they necessarily have different positions, which leads to less electrostatic repulsion. This is my qualitative understanding of the issue, and it is also--to my understanding--responsible for the phenomenon of exchange energy in half filled shells.

(Filling out orbital diagrams in this order has become intuitive to me after three years of undergraduate chemistry, but I guess I rarely step back and re-rationalize why it's the case).

So coming back to paramagnetism. This means that if those two electrons have the same spin, there is a permanent magnetic moment in the molecule (right? but what what is a magnetic moment anyway?!?! crap.) which means that it creates its own magnetic field. I recall the Lorentz Force law from physics (is this even exactly related?) although much of what I remember from electricity and magnetism involves a lot of fussing around with the right hand rule and being confused by which direction my thumb went. Anyway, if there is a permanent magnetic moment when put in an external magnetic field, the magnetic field can be parallel and thus be attracted. Whereas when a diamagnetic species is put in a magnetic field, since there are two electrons going in opposite directions, one of the vectors must necessarily oppose the magnetic field.

Okay, this makes sense, although I'm sure I butchered a few of the details. Then there's something something angular momentum vector something something spin momentum vector something something more quantum mechanics something something. But then I ask myself what is spin really? Why does it run parallel to the magnetic field. Why are parallel magnetic fields attracted to one another? Does it just have to do with the orientation of the electrons compared to the nucleus? WTF? Wait, wait, this was all beginning to make sense, and now it's all falling apart again.

So I waste hours of time on Wikipedia physics pages being confused.

It's funny that we use the same language as people who actually have a deeper level of understanding of these phenomena, but don't actually understand it at a deep level at all. It's all about shorthands to understand the parts we need to understand--in this case--for chemical reactivity and understanding MO theory.

The more chemistry I learn, the more of a head-case I become.

Junior Qualifying Examinations

2009-04-07T10:43:00.000-07:00

So at Reed you have to pass a junior qualifying examination before you can register for your senior thesis. As an interdisciplinary major, I had to take both biology and chemistry. Biology was an open note/book/internet exam basically based on my coursework. I wrote an essay about haploinsufficiency in Marfan's syndrome fibrillin-1 gene and the elastin gene in Williams' syndrome and another essay where I wrote about the growth hormone axis and how nutrition (both being malnourished and obese) affected this axis. I also did some quantitative questions like calculating Tms of DNA strands and making buffers. I should hear back about it soon, although I'm afraid I might have gotten a conditional pass from messing up calculating TRIS on that buffer question, eeek. It's not a big deal if that happens, I just need to fix what I got wrong.

The chemistry qual was an oral exam where I was given this paper and had to learn as much as I could about it in 48 hours. Then they asked me questions, specifically about the paper, but really probing my organic chemistry knowledge as a whole. I had two options, an organic option and a biochem option, and I decided to go with the organic option. The biochem option was interesting too, it was on nicotine binding in the brain and how it is different from its inhibitory effects on your muscles (if it did hit the receptor in your muscles you'd be dead). But ultimately I felt more comfortable with the sort of questions they would ask in an organic qual, especially since my advanced synthetic final last semester was in the exact same format. Luckily, my organic paper was a synthetic paper and not a mechanistic paper--because for some reason the long lists of data tables with numbered compounds in mechanistic organic papers followed by colums of de's and ee's result in my eyes glazing over a lot of the time.

I think it overall went well. A lot of the questions were definitional--what is the kinetic enolate vs. thermodynamic enolate, what is an allene functional group, what is "latent stereochemistry". The main places I got tripped up on were mechanisms. I had this divinyl oxy-anion cyclopropyl Cope rearrangement mediated by a Brook rearrangement, and I started off drawing the reaction in a different perspective than I had in my notes which kind of threw me. The paper went to great pains to discuss why this enolate attacked from the more sterically hindered side (because it was reversible and resulted in the more stable transition state for the subsequent Cope) but to demonstrate it only showed what didn't happen due to steric repulsions--so there was no picture to look at what did happen. Which I knew, but it's just sort of difficult to pull all of that together visually on the board with weird bicyclic systems and the boat transition state and so forth. It went ok, I just had a moment where I was like "wait Connie..."

The other place I got tripped up due to nerves was the mechanism for oxidizing an enolate with a Davis oxaziridine. Again, it was ultimately ok, just a little bit of nerves. Also drawing 7 and 8 membered rings on the whiteboard was tricky!

The spectroscopy portion was easy since they had already assigned the peaks in my paper and my profs didn't ask me anything too difficult. Just like, why methyl groups attached to silyl groups were more upfield than methyls attached to carbons and whether this one set of diastereotopic methylnes were chemically equivalent or not, and why they had different J-values coupling to a neighboring proton that sort of thing.

It also struck me last night that wow, college has crammed a lot of chemistry into my head in the past 2 years.

So I should be hearing back about whether I passed, conditionally passed, or failed those shortly.

Nature Chemistry and Twitter

2009-04-01T19:49:00.000-07:00

This month is the first issue of Nature Chemistry, and as far as I can tell they appear to have some sort of free preview for the first issue because I'm positive that Reed doesn't have access to this journal, but I've been able to access the full text PDFs. It seems like a good read, although I haven't had a chance to look at it all that thoroughly.

In addition, I have learned that all the major journals AND sigma aldrich have twitter feeds. As if I really needed to know about the latest advance in chiral chramotography in a two line twitter blurb, heh. It's sort of an interesting form of information flow, because I've noticed that this sort of abstract of an abstract catches my attention occasionally in ways that my RSS feeder doesn't.

I also learned that Nature Protocols gives out the occasional free featured protocol. This week it is how to produce silk-like spider proteins recombinantly. Which I'm sure has a lot of relevance to my life, but anyway, it's kind of cool that you can get random protocols without paying $500 a month. So if you were ever curious about how to make and purify spider silk-like proteins, you're in luck, I guess. I learned this from twitter as well.

On being an o-chem lab TA

2009-04-01T19:41:00.000-07:00

It's very funny to me; all of a year ago I was a struggling sophomore messing up the very most basic of things in organic lab. I remember feeling frustrated, feeling like I was bad at lab, feeling like I was one of "those kids" for the prof and the TA.

Now I am a lab TA for organic, and it's all very automatic. I can anticipate the questions before they come; my eye gets drawn to certain very specific mistakes. It's usually things like "no you're sep funnel isn't broken, you just need to uncap it before running it down," or "by the way, your reflux condenser hoses are connected backwards," or "you don't need to heat that--25 degrees is room temperature," or "do more polar things run higher or lower than less polar things on silica gel?" or "is water more or less dense than most organic solvents?" or "you should really put boiling chips in that".

Furthermore, when people ask me for NMR help, it's funny what seems so obvious now. Like common solvent peaks--being able to just identify ethyl acetate or isopropanol or ether. Just knowing what shifts and J-values are characteristic of what.

I guess I can see how some of my professors are the way they are after, you know, 40 years of this.

Molecular computing: logic gate

2009-03-15T00:49:00.000-07:00

This is pretty neat: it's a molecular logic gate. It senses pH, sodium concentration, and zinc concentration, and if all three are present, it fluoresces. I just found the concept to be pretty clever. The molecule looks like this:

J. Am. Chem. Soc., 2006, 128 (15), pp 4950–4951

DOI: 10.1021/ja058295+

2009-02-18T19:02:00.001-08:00

I am so fucking tired. My god. I don't know how I managed to get this sleep deprived.

The semester goes ok. Physical chemistry is giving me some demons because I suck at math. That last stat therm test was pretty brutal. I hear Dan's tests are always brutal though. Anyway, it's just going to be something to get through.

I don't have much structured course-time as I am only taking one lab class but a lot of homework all the time. I'm also working on something in one of my profs labs so in between classes I'm usually running reactions and working things up and taking NMRs and so on. Squeezing in time in the lab on top of a full load of classes is a completely different matter than having seven or eight hours during the day to just do chemistry like it has been doing summer research. It's making me really excited for thesis next year, though.

I love being in the lab doing projects. What I don't like are class labs. It honestly just feels like a huge waste of time to spend eight hours taking data that no one gives a fuck about and has been done thousands of times before and will yield crappy results and then spend another ten hours writing some bitchy-ass stupid lab report where you have to anal-retentively propigate all the error and so on. It's just biochem methods and analytical that I have to get through still and then I am relieved from stupid lab classes. I guess I see why they are useful and necessary, but by junior year you just sort of feel done with it. I want to be in lab the doing research and not doing annoying pedigogical exercises. The exposure to lab techniques is good, I guess, but I almost feel like I'm at a point where I can pick up most lab techniques as necessary.

I've also been thinking more and more about applying to grad school next fall. Basically, I just want to be in a situation where I am discussing and learning about science at a high level and being in the lab. I've always thought I would take a break between grad school and undergrad but I'm starting to think that I'm ready to move on to that phase of my life.

quantum mechanics won't solve all your problems

2009-02-07T11:31:00.000-08:00

It took three years of chemistry education, but I think I finally understand what a wavefunction is and what quantum chemistry is. While I have very little native interest in the process of integrating over all space and solving differential equations to reach quantum mechanical approximations (I'd rather appreciate the fruits of other people's labors in that area...or get the computer to do it), I think I finally get quantum chemistry is all about conceptually (and why it is very bizarre). I think having calculus, statistics, and physics really solidified all of this for me--even if I can't do the math facilely operationally, I do know what a differential equation is, what the dot product is, why probabilities have to integrate to one, what the complex conjugate is, and what polar coordinates are...and Dan, Maggie, and Alan have given me a pretty solid conceptual idea of what the mathematical gears behind orbitals and energies are.

Depending on what I do later in life, I may or may not need to confront all this at a higher level, and beyond just a conceptual level, but I think I'm content now with the fact that I'm not going to have time to take it before I graduate.

2009-02-01T23:41:00.000-08:00

I'm feeling better about my life choices right now. Working on my inorganic chemistry problem set--and I realized that this class is really fucking cool. It gives you just enough quantum mechanics to appreciate what quantum is and what the beauty of it is. I mean, I know that at some level I knew what orbitals were, but it's kind of neat to see a function (even if we're not going into the nitty gritty details of the mathematics) graphed in polar coordinates and suddenly an orbital appears.

I'm also feeling better about the freakout I had on Friday where I wished I had been a straight chemistry major. Because effectively, I've taken pretty nearly the same courses as a chemistry major but I also know about as much biology as a biology major. I'm a little deficient in the math department, but I do know a lot of science.

2009-02-01T15:16:00.000-08:00

I'm a lab TA organic chemistry, and tomorrow they are doing Grignards. Hopefully no one will point the heat gun at a flask of ether. It should be exciting times, though.

There's so much to chemistry

2009-01-30T23:09:00.000-08:00

Basically what this semester seems to be boiling down to is physical and inorganic chemistry are waaaaayyyy different from organic. Jesus christ.

I've been fussing around trying to calculate the numerical radii for the radial nodes of a 3s and 3p orbital for frickin' ever.

and so it goes

2009-01-28T15:19:00.001-08:00

Today I decided to drop my biology seminar in favor of keeping all of my chemistry courses. I'm feeling good about this decision, and I have a tough semester ahead of me but I really like all my courses (well, besides stat therm, but stat therm is a necessary evil), and regardless of whether or not it's more or less work than my other classes, it is one more thing to keep track of. The course is offered every year so I can take it next year, and bio seminars are good courses to take as a senior. I haven't attended it yet, which makes it easier to drop, and I really like my advanced mechanistic organic chemistry class. Advanced mech only has 5 people in it which gives it a nice small feel, and overall it's just a fun course. Which means I'm taking all chemistry courses, and only 3 units (technically). Inorganic (even without the lab) and stat therm in particular are highly time consuming courses and not going to seminar on Wednesday nights gives me more time to hammer through psets and study for them. I have a good feeling about this semester; not taking any biology courses is going to be a little weird, but whatevs, at least I have biochem.

It also gives me more time to play with my little project (although PEOPLE KEEP USING THE COMPUTER LAB SO I CAN'T USE SCI-FINDER! grrrr).

Onto making flashcards to help me memorize the periodic table for inorganic.

2009-01-26T23:42:00.000-08:00

I feel like my rather shitty math background has been a constant handicap. Due to the fact that the math department at Reed only teaches theoretical math geared towards math majors, and due to the fact that Rao (the math head) determined my semester of calc I at UIC as equivalent to Reed math 111 (calculus), I have managed to skate through Reed college only taking probability & statistics. Because of this wacky math system, math 112 is more introduction to proof writing than a calc II course, and I was told that unless I was really into theoretical math it wasn't going to be fun and it certainly wasn't going to be useful. I never took calculus in high school and I didn't want to push physics to my junior year (thank god I didn't).

Due to this situation the chemistry and (especially) the physics department pick up some of the slack. Yesterday I learned how to take a second partial derivative with respect to two different variables. Having never taken a multi class, I picked up the concept of a partial derivative and how to do it in intro physics when learning about the wave equation. I had never seen the notation for a double partial derivative before. I'm a little shake on integral tricks too.

I'm usually ok with this fact, and I've kind of accepted that I'm more prone to think about the world in descriptive terms. This doesn't mean that I'm not down for a few computations, but I'd rather plug it into a modelling program or mathematica. I'm good with scooting around arrows, stability rationalizations in the style that organic chemists do it, and basically things that operate in pictures and words with small amounts of algebra and maybe a derivative or two. I love to learn about biophysics and I think the techniques that are out there are quite fantastic, but my understanding of them is all in pictures and words. Same goes with NMR. My feeling for the physical world is one where math is a tool, but I'm not interpreting it through it. I see math is a way to get better pictures in my head. This is at a stark contrast to the way physicists--and for that matter, even physical chemists--seem to view it--as if they interpret physical phenomena through math.

I'm re-learning about the quantum numbers for inorganic (I learned it in intro chem once but forgot) and there's always something in the book like "you can solve the Schrodinger equation for hydrogen and hydrogen-like nuclei, but we're not going to go into it in here" and sometimes it makes me feel bad about not taking quantum. It's like, even though I did quite well in my synth class, I feel like I don't have quite the feeling for what is all behind it as some people. I know that what I learned in intro physics I generally rarely use beyond bits and pieces here and there, but it was good for backing up my general physical intuition and understanding for how things work. Conservation of energy, waves, momentum, acceleration, electric and magnetic fields, these are all fundamental things that I need to understand as any sort of scientist--and are even helpful conceptually for biology. Ploughing through it all, I can't really do those problems anymore but I left with a better conceptual understanding of the physical world. Dan reminded me the other day that physical chemistry does this for other types of chemistry, i.e. the pictorial representations of stability rationalizations are quantifiable (well, sometimes) and that's where the theoretical basis for these qualitative observations come from even if we don't always have the computational power and models to find them quantitatively. It doesn't mean I have to want to be a physical chemist, but I do realize the power in other chemical approaches and understand why I need to learn about them.

I think a lot of my issue with math is a lack of confidence from being "bad" at it for so long. I mean, calculus is a tool like algebra and not like WHOA COMPLICATED OMG MAGIC!

On the up side, speaking of nice, fuzzy picture-based synthetic organic chemistry, Pat gave me a little project to mess around in the lab with. He gave me a couple compounds he'd like to make and test the pKas. I need to go play with Sci-Finder to see if they have been made before. This is good; they're small molecules and models for the types of compounds the lab as a whole works with, but in the past the research I did with him was more guided like "here's this idea I got, I'd like you to try it out" instead of asking me to find preps that I might be able to run. I also know more chemistry and know how to use Sci-Finder better than I did when I worked for him last summer, though.

First day back

2009-01-26T18:30:00.000-08:00

As predicted, my chemistry courses are pushing me out of my comfort zone. Inorganic and stat therm are totally different types of chemistry from what I'm used to dealing with. Even adv. mech is pushing me out of my comfort zone with some tough Diels-Alder structures. I'm ok at seeing them retrosynthetically (I think probably from reading Totally Synthetic)--but for some reason the product picking and remembering the endo rule is harder for me to put together since I don't have much experience with dealing with pericyclic reactions. I also realized that I don't know where anything is on the periodic table besides...uh..most of the first two rows. I don't know what Maggie is going to think on my pre-quiz. If only I could take solely organic chemistry classes...

I had a minor flip out about not being mathematically prepared enough for stat therm after working through some calculus review Dan gave us. Also not knowing how to do double partial dervitives with respect to different variables. He sat me down and showed me how to do it and assured me that the calculus would not be my problem--it would be the algebra and the concepts and that I had a decent grasp, even of partial derivitives. I also had an involved conversation with Alan about various things, including things posted the other day, and about how he and his wife coordinated their careers.

I feel so much more at home in the chemistry department than in the biology department like 99% of the time.

Musings about being a woman in science

2009-01-25T18:30:00.000-08:00

Again, the fact that I have so much time and intellectual energy to spend writing my thoughts in this blog indicates that it's definitely time for classes to start again (they start again tomorrow...9 am statistical thermodynamics).

One thing I've been thinking about lately is the idea of how difficult it is going to be to have children if I pursue a career in science. Clearly women do it. My roommate's PI at Oregon Health Science University has a daughter. At my school--which is a liberal arts school and not a hardcore research university to be fair--there is one woman chemistry prof who has two children and three women biology biology profs. Only one of the three women biology profs had a son, although one of the three is in her early 30s and just got on tenure track a couple years ago. (Tangentially, it's remarkable how few women faculty members there are in the sciences that is now that I write that out).

People write about how academia is notoriously difficult for women if they want to have a family because there is no good time to get pregnant. By the time you finish your PhD and post-doc, you're already in your early 30s and not in a position of job security. I've heard of people having kids while they are in graduate school, but usually men. My friend and his brother grew up as little kids on graduate stipends (he said his parents always felt guilty about being unable to provide for them well, but they felt like having macaroni and cheese for dinner every night was awesome--you don't notice when you're a little kid). But the thing is there's no way in hell it would be responsible to carry a fetus while doing lab work, especially in synthetic organic chemistry. I mean, I'm just thinking about the amount of chloroform I inhale while running a column, even when using the hood correctly. That means that you have to take, essentially, a whole year off of working if you want to have children. I'm not sure how other careers--like industry careers--are affected.

My mother was an environmental scientists and worked for the EPA when she had me and she basically worked throughout her pregnancy. She at one point did toxicology stuff and would go to the dump to take samples, but she did other office-based work as well that allowed her to do work that one can safely do while pregnant when she had me. After my brother was born she took time off and returned briefly when we got older, but stopped working again when we moved when my dad got another job. She's now an artist and works on Go Green Wilmette, the local environmental effort in the town we live in, a suburb of Chicago. She said that she sometimes feels guilty for not providing a better model for a working mother, and that we don't understand that the field she was working in was highly male-dominated and that she was one of very few women to work in environmental science in the '80s.

She said on the other hand, though, she didn't want us to be raised by nannies. If she was going to have children, she was going to do it right. I grew up in DC until we moved when I was ten, and there are plenty of families with two parents that had high powered jobs and I knew plenty of kids who saw more of and were more attached to their babysitters than their parents. I have a lot of respect for my mother, and I don't think her choice was a bad one or a weak one. I think that I was raised well, that my parents are intellectually curious people who instilled some of that curiosity in me, and that, although I don't agree with 100% of their parenting choices, they are a pretty good model for how I want to raise my children someday.

I'm at a stage in my life right now, unlike some of my friends, where I don't have a serious long-term relationship yet. A few of my friends are trying to coordinate post-graduation plans (whether it is grad school, Teach for America, or employment) and while enough of them manage to work it out, it seems to be a huge headache--especially for graduate school. One or the other person usually has to compromise or else they're doing long distance for 5 years, and I imagine it doesn't get any easier after that. One of my chemistry profs and his wife worked it out nicely where he works at Reed and she works at Portland State University and they have children and each have tenure. Two of my friends worked it out for REU programs last summer, but it was stressful and one of them had to compromise by going to a (very good but) less competitive program than the best one she got into. It gave them a serious taste of how it would be when they both applied for PhD programs...

More of the girls I know--even as an undergrads--are paranoid about planning their lives and their careers. We think about these consequences way more than our male peers, and we wonder about how taking a path that takes a lot of training--like getting a PhD--affects having a family. This is the main argument I see for jumping into grad school directly out of undergrad.

Edited to add: this New York Times article has some interesting statistics. Excerpt:

Surveying outcomes for 160,000 Ph.D. recipients across the United States, the researchers determined that 70 percent of male tenured professors were married with children, compared with only 44 percent of their tenured female colleagues. Twelve years or more after receiving their doctorates, tenured women were more than twice as likely as tenured men to be single and significantly more likely to be divorced. And lest all of this look like “personal choice,” when the researchers asked 8,700 faculty members in the University of California system about family and work issues, nearly 40 percent of the women agreed with the statement, “I had fewer children than I wanted,” compared with less than 20 percent of the men. The take-home message, Dr. Mason said in a telephone interview, is, “Men can have it all, but women can’t.”

Also, this article addresses the issue with some interesting data on it as well.

Eh, future

2009-01-25T15:45:00.000-08:00

Posts like these make me scared--because being a "jack of all trades, master of none" is basically what I have been on track to be through all of my undergraduate education (this whole BMB business with extra chemistry classes). The PI who I sent my CV to who I will be working for this summer saw this as a good thing; he was impressed by my desire to do interdisciplinary research and my varied experiences in the lab. At Reed no one in the chemistry department seems to remember whether I'm a chemistry major or a BMB major because I spent the summer doing organic synthesis. I've been skating between the two departments and following my academic wanderlust since I got to college, and imagine myself doing the same afterwards.

But I worry. I have a few subjects that I am strong in and can be very enthusiastic, but I'm aware that the world is full of people smarter than me. My main strengths are enthusiasm, my breadth of curiosity, and the ability to get very interested in projects. I'm a good student, but not a great student and my transcript is far from perfect. I'm not really cutthroat and when I do well it's because I find some little area that interests me and just dive into it. There's a couple issues at play here: I know I love science enough to want pursue it further but a) do I look good enough on paper to get into good graduate programs? b) where is my place in the scientific community going to be? and c) am I of a competitive enough disposition?

While I feel like I have as solid of a training in organic chemistry as a chemistry major (what classes will I be missing when I graduate? quantum chem and physical chemistry lab) and as solid training in molecular biology as a biology major (I'm missing the population/organismal/evolutionary class requirement), I'm just definitely not (at least right now) approaching it in the traditional "get a grounding in one field and diversify from there" approach at all. The "what the fuck am I doing with my life" question is one I've thought about a lot, and generally all this sorts itself out so I'm not that concerned. But it seems like everyone has a different opinion on what the best way to go in the interdisciplinary sciences is in terms of training, where everything is headed, etc. Also--this is just undergrad--my professor likes to tell us that he studied chemistry (primarily inorganic) in undergrad, got a PhD in organic chemistry, did his postdoc in a physical chemistry group, and now teaches biochemistry and likes to emphasize that--at least in academia--you're constantly re-inventing yourself. My profs keep telling me that no one cares what your degree is called--they care about your research experience and coursework.

I also know I have a full year and a half of school left to ponder these things, and I will likely take time off after that. Fretting is not really productive, and life is full of surprises and changes of plans.

Coffee: good for your brain

2009-01-25T14:42:00.000-08:00

And now for some science in the news: Drinking 3-5 cups of coffee a day leads to a lower risk of dementia later in life! It decreases your risk of Alzheimer's and has also been associated with a lower risk of type 2 diabetes and Parkinson's.

I love reading articles extolling the benefits of my deep addiction.

Polyketides again

2009-01-25T13:09:00.000-08:00

I've been thinking lately that I would like to go into polyketide chemistry, lately. I'm going to work in a lab this summer that works with bacterial polyketides, and as far as I can tell, the whole field pretty much brings my all my interests together. Even in light of what I said about combinatorial chemistry (and in this case, biology) which is an aspect of playing around with biosynthetic genes.

It's one area of chemical biology that has caught my interest this year (which is basically when I started browsing the chemical biology lit). It relies heavily on organic and bioorganic chemistry, but also genetics and even tracing evolutionary pathways (like this review that talks about how the classifications of polyketide synthases are a little rigid). There's a med chem/natural products discovery aspect to it, since a lot of these structures are really promising medicinally as antibiotics and chemotherapeutic agents (and like I posted yesterday, the genome-mining approach). There's a synthetic organic aspect because a lot of these structures are good targets for total syntheses due to their medicinal qualities. There's an enzymology aspect because a lot of these biosynthetic enzymes have really interesting proprieties. And then there's even some work on trying to harness enzymes that do mechanistically biosynthetic transformations hard to emulate with classical reagents for use in total synthesis, like this total chemoenzymatic synthesis. There's a structural biology aspect too--like this paper looking the structural basis for polyketide synthases docking and substrate specificity. I suspected there would be some biomimetic organic synthesis based on some of these bacterial polyketide biosynthetic pathways out there, and a quick google search told me that there's is, indeed, loads of work being done in that area.

I've started bookmarking webages of labs that publish in this area (and other areas that look interesting) because...well, I figure if I still want to go into this (kind of specialized) area by the time I decide to apply to grad school in a couple years, that's probably a decent approach. It just seems like such a promising area for me and for my desire to bring all these interests of mine together. And just to see where it goes generally. It's not a cutting-edge new field, but just a field that keeps getting cooler and cooler as our tools to do science get cooler and cooler.

Knowing vs. Finding Information

2009-01-24T15:28:00.000-08:00

One thing I think my generation is very good at is finding information. Not necessarily knowing information off hand, but being able to sift through search engines and databases and find what we want. People of my parents' generation keep complaining that we can't do basic math, we can't spell, and our handwriting is atrocious. But my parents are amazed at the speed at which I can retrieve information off the Internet. (Part of it is that I waste an atrocious amount of time browsing--but I do discover a lot of new neat shortcut Internet applets and webpages this way).

Now in light of science education and science as a whole, I'm not sure where this puts us. I have a really hit or miss memory (I either know extremely detailed information or I totally blank out), and memorizing enough information to do well on exams is a chore. I mean, I'm glad I was asked to memorize the amino acids in biochemistry, enough basic organic reactions, and enough pKas to be able to guesstimate most pKas of organic materials because it does help with my fluidity in understanding papers and talks. It's not that I'm incapable of memorization--I'll do it. I'm supposedly "good" at things that people traditionally associate with being memorization heavy, which I contest are more problem solving. In fact, the way I studied organic chemistry was by stringing together the reactions in goofy synthesis problems of partial structures of psychedelics that I looked up on wikipedia or just some molecule I thought looked cool that I made up. I would make up practice problems for my friends--and this would give me a chance to think about the problems retrosynthetically and when I got to a problem on a test I was used to thinking about a variety of sequences that would be useful for making and breaking bonds and had several strategies for this laid out in my head. I talk to a lot of my classmates who also did well in that class and most of them tended to take a more conventional flash card and practice problem approach. I did some practice problems and flash cards, sure, but every now and then I needed to make it more of a game to maintain my interest. It probably has something to do with my ADHD--I try to turn studying into games because when I'm engaged I go into hyperfocus mode which is really conducive to studying, writing papers, or lab work (ADHD can be a curse, but also a blessing). This is a tangent, though.

My ability to retrieve information came especially in handy in my advanced synthetic organic course when all of our exams were open book and taken straight out of the lit. The problems, then, were extremely difficult, but that meant that I could focus on categorizing information and developing strategies in my head for how to put it together rather than storing it, which is much better for my learning style.

Given the great abundance of information available to us, I'm not even sure that knowing information off-hand is even all that useful--especially in very interdisciplinary fields. I think it's more important to be aware that information exists and then be able to retrieve it quickly or ask another person who is an expert. Learning how to critically think, to research, to evaluate, and to organize information is important when you have endless sources of it at your finger tips.

Honing these skills, obviously, is not always a practical approach for a lot of classes geared at giving you a basic background in the subject, though, and I'm not sure how to reconcile this. I also see how you should very detailed information about a project you are very close to, like a thesis. But in terms of a general knowledge base of scientific literacy? I still contest that it's more important to know how to find information in this day and age.

Incidentally, a friend of mine who is a classicist said similar issues came up in their field when the Perseus Project went up. It meant that they didn't necessarily need to memorize as many strict grammatical rules and vocabulary since it was hyperlinked in the text, and revolutionized the way students would go about reading ancient texts. So the question of "how much information is necessary to hold in your head compared to what has conventionally been deemed necessary" is not unique to science. I guess in some ways it's akin to the fact that people stopped memorizing whole epics to perform orally after the printing press allowed books to become widely available and people talked of the demise of the oral tradition. In reality it just led to a whole new set of opportunities in literature.

Genome Mining for Natural Products

2009-01-24T13:29:00.000-08:00

I've discovered a lot of interesting science in ChemBioChem, a European chemical biology journal. We have more access to more of these journals than most of the Nature journals; it must be because there is some relatively cheap Wiley journal package that comes with Angewandte Chemie, since we basically get all of the European chemistry journals that are published by that group.

But in any case, one pet area that has been fascinating me lately is the convergence of genetics, microbiology, analytical chemistry, and synthetic chemistry to the discovery of new natural products, especially in examining modular biosynthetic polyketide genes. This review that came out a few days ago, Strategies for Discovering New Natural Products through Genome Mining, went through basically what is being done in the field.

The authors explain that natural products discovery has not been favored by pharmaceutical industries for a while as a way to discover new drugs. Most of the 20th century (after penicillin was discovered) is described as the golden age of antibiotics and natural product discovery. It has fallen out of favor because it is time intensive and often leads to discovery of natural products that are already known.

But now, in a post genomics era with so much bioinformatic data out there, we actually have new strategies to approach discovering natural products, especially in examining biosynthetic gene clusters. We can search for PKS (polyketide synthase) domains, we can knockdown genes, and (most exciting to me) you can reconstruct products in vitro to determine if that gene cluster is actually making what you think it is (and then confirm what you have with NMR and MS). Of course, with the reconstruction strategy there are certain problems, like finding the right promoter and so forth, but chemoenzymatic total synthesis to reconstruct biosynthetic pathways has been done in vitro before.

Polyketides are neat from a pharmacological standpoint, because the secondary metabolites tend to have a lot of medicinal properties. They are also neat in that a lot of the genes are modular, so there have been some papers where they re-arrange them essentially doing synthetic chemistry in a cell instead of in an RBF. And sometimes they have neat little genes beyond just PKS genes--I recently wrote a paper for school reviewing research on a gene that was responsible for doing a powerful oxidation to form a chiral THF ring. It seems like a way to both discover new natural products with pharmaceutical value and to generally get a better mechanistic grasp of biosynthesis.

Combinatorial Chem

2009-01-23T18:48:00.000-08:00

I've been reading about combinatorial chemistry lately, especially its applications in drug discovery. Last semester Jordan Katz (a Reed alum who recently finished his PhD) gave a talk about using a combinatorial approach to find the right inorganic materials for solar cells--unrelated to drug discovery, but showing that it is a useful technique in a variety of applications. This paper and this paper aren't exactly new, but they were my first introduction to the idea of screening a modular library that utilized a combinatorial approach (papers read in my topics in biochemistry course this past fall).

I think I understand the utility of such an approach. Biological systems are complicated, and the idea of design feels really...strange in some ways. Nature works through selection, not design. I know that there are drugs that have been designed, but I can see how a combinatorial approach would be a useful angle since there are so many potential compounds that could be pharmacologically active (is "chemical space" the right term?).

But every time I read a paper that uses a combinatorial approach, all I can think is how boring it must be for the poor grad student or lab tech carrying it out, since it's a conceptual problem that takes a lot of hands going through tedium to sort through. I think at an abstract level, design is more appealing because it is just more satisfying conceptually to think through a rational structure. At least, as a reader, it's more satisfying to read about. I can't help but find combinatorial chemistry boring, however useful of a tool it may be.

This Upcoming Semester

2009-01-23T15:55:00.001-08:00

I'm enjoying these last few days of basking in winter break (classes start up again on Monday); browsing the Internet endlessly and guilelessly, watching TV on my computer, and drinking with my friends. But I'm gearing up for the start of a new semester that will hopefully be good.

Between my theoretical organic chem class (advanced mechanistic organic chemistry) and my intro inorganic class, I'm hoping that MO theory might actually make some semblance of sense. A professor described it once as "chemistry's version of the stork story", so I'm aware of some level of fundamental bullshit going on in describing orbitals and chemical bonding, but I'd really like it to be a little more coherent in my head conceptually than it currently is. When I tutor organic chemistry sometimes I feel like a total faker, drawing meaningless balloons and calling them a HOMO and a LUMO. I understand it well enough to sort of describe what's going on in the Diels-Alder, but just barely. I've been introduced to some ideas that are useful mnemonics for stereochemistry and useful to know to generally understand what's going on in the lit in synthetic organic chemistry (concerted reactions, thermally allowed vs. photochemically allowed, chair like transition states, etc.). But apparently this class goes really into the Woodward-Hoffman rules, and I imagine that conrotatory and disrotatory will mean a whole lot more to me after the end of the semester than it does now. I'll also get a better grip on how to use Spartan, which will be good because computer modelling is useful and not something I am terribly comfortable with.

I'm hoping that i-chem will fill some gaps I currently have in my chemistry knowledge. I felt both in synth and in biochem that some things would have made more sense having more background in inorganic. In any case, the textbook looks pretty interesting and it's a chance to do some totally new chemistry. Along getting a better grip on MO theory, I'd also like to get a better grip on coordination chemistry and remember that d orbitals actually do exist. And to be reminded that there are chemists who don't view carbon as the center of everything and who regularly look beyond the first two rows of the periodic table.

Statistical thermodynamics, my physical chemistry course, looks pretty gross. I know I shouldn't be closed-minded, but I was flipping through my book and saw the return of angular momentum and it gave me chills flashing back to intro physics. I know I'll get through it and I know I'll appreciate it in retrospect, but...it'll be a slogging through it experience. It's going to be a lot of math--and I'm much more into the descriptive aspects of chemistry, or at least that part comes a lot more intuitively.

It's going to be a very chemistry-intensive semester; I'm only taking one biology course and it's a seminar on membrane-membrane interactions that meets twice weekly run more like a journal club than a class, not a full lecture-lab course. This is the first time I've taken so much chemistry at once and I hopefully won't OD on it. It's also pushing me out of my chemical comfort zone of pushing around arrows, but that's probably a good thing.

I'm also excited about my independent study. It's a not-on-the record, not-for-credit thing, which is good because it means I can do as much or as little on it as I have time for. I'm not sure exactly what my synthetic target is going to be, but I've worked in that lab before and the research done in there is ongoing, so I'm familiar with the overall project. I'm going to chat about it with Pat (the prof whose lab I'm working in) on Tuesday to work out some details. I'm not sure if I'm going to continue to TA organic lab this semester or not. I was asked for my availability, but I think it depends on how people's schedules work out. I'm also only taking one lab class--biochemical methods--which is the first time this has ever happened in college. In the past I've always taken two or three labs at once.

I have to take my quals this upcoming spring. Reed sort of mimics the PhD system and junior year you have to take junior qualifying exams in your major before you can register for your senior thesis. As an interdisciplinary major, I need to take both the biology exam and the chemistry exam, so that's going to be two intense weekends this spring.

And then...wow. Next year I'm going to be a senior. Next year I need to take analytical chemistry, one more liberal arts course to fill a group requirement, and my thesis and then I'm allowed to graduate. Crazy times.

Liberal Arts College vs. University

2009-01-23T14:22:00.000-08:00

I am very much a proponent for a small liberal arts school science education. I have no idea how I will fare later in life, but I have no doubts that my education has been anything but excellent, and, on the whole, superior to my friends' educations that go to large institutions.

See, even here I had some large lecture-based classes that kind of sucked. Introductory chemistry was ~120 people. However, even with 120 people in the course it was a) taught by a professor b) all our exams were graded by him (even if he hired student graders for homework and lab reports) and c) he knew every one of our names. Even then he was down for p-set help and just dropping by his office to chat. And this particular professor is what drew me into the chemistry department in the first place. Later my courses got smaller and more specialized, and I suppose that is the case anywhere.

My friends at Berkeley, University of Illinois, and other large research-focused institutions describe to me gen chem and even organic chem classes as being ~500 people. My sophomore organic class was 70 people, and this was considered abnormally large (usually it's closer to 50), and definitely much larger than the average Reed class. They also describe this trend towards making it more interactive involving clickers that digitally record answers to multiple choice questions on the screen, which in reality is an easy way for the TA to take attendance (which I think is silly; we're all adults now, the only person you're hurting is yourself--unless you don't get anything from going to lecture anyway--and then what's the point?). Students get around this by getting their friends to go to class and press their respective clickers for them, and take turns who goes to class just to press the clicker enough to get participation points.

My friend Luke is in the aerospace engineering program at the University of Illinois--which is a great program, one of the best in the country--and he says the big advantage is that in a couple labs they got to go see real planes and play with the mechanics. You just don't have those sorts of facilities at a smaller institution. But he said he also did not know a professor well enough to ask for a recommendation when applying to summer programs and he has no clue what he is going to do when applying to graduate school. He said that he often feels that the access to larger facilities in the end doesn't outweigh the benefits of having mentors relationships with professors who know you personally considering how infrequent access to these facilities are.

I know I certainly complain enough about Reed not having subscriptions to Nature Chemical Biology or Nature Reviews Drug Discovery, and I would have access to that at someplace like, say, Berkeley. I also know that if you are an undergrad confident, savvy, and lucky enough to ask and land a research position then you get to do things that we can't do here. Our science is modest; sound in methodology, but far from cutting edge. Profs publish, some more than others, but not that often. I know that if you are bright and self-directed you can make use of the facilities and resources of being in a larger institution, but in all honesty, it seems like most undergrads get lost in the sea. It also seems like anyone who is extremely self-directed does a fair bit of teaching themselves things; and while I'm all for self-teaching, it makes me question what the point of having class is. If the syllabus is online, if you have libraries full of books and journals to read, and if you can check your answers against an answer key, no wonder people at larger schools skip class. I always found that self-directed learning is great, but complemented by really excellent teachers.

I am sure there are some students who are better equipped to deal with bigness than I am. But I feel like for most of us, we're still figuring our shit out and we need more interaction to keep us from just skating through. I feel like I am solidly accountable for my work, and no one is just shuffling me through the system, and like I am getting trained to think like a scientist. Yeah, Berkeley has some sweet facilities, but it's not like I would get a chance to use them as an undergrad in all likelihood anyway.

Flourescent Protein Timers

2009-01-22T14:45:00.001-08:00

Since Reed doesn't have a subscription to Nature Chemical Biology (I guess I could Interlibrary loan it if I'm really curious--but I still find that incredibly annoying), I'm stuck reading other blogger's accounts of the cool research in there. Like florescent proteins that work as a timer. As far as I can tell, they change color temporally, making them potentially a really powerful tool for cellular tagging and localization studies.

Seriously, though

2009-01-21T18:28:00.001-08:00

Apologies for posting here so much; I'm on the last few days of winter break and have the time to do so, I suppose and I'm going a little stirr-crazy.

I was wondering if there are better RSS feeds than the one I have for PNAS, Nature, and Science. All of my ACS journal feeds are quite nice; it gives a full abstract as well as a graphical abstract and makes browsing really easy. And I recently managed to dig up a better feed for Angewandte Chemie (mostly due to reading chemistry blogs of other science people who spend far too much of their life on the interwebs). But I can't find an RSS feed for Cell, and Nature, PNAS and Science suck. No abstract, no nothing but the title and authors. Do biologists spend less time dicking around on the internet? I doubt it. There is way too much down time in molecular biology for that to be true. I gotta do some surfing around to find them.

Unrelated, but I also found it interesting that there was an extensive review article about RNA interference in Angewandte Chemie the other day. The borders of biology and chemistry are becoming very fuzzy indeed.

On Chemical Biology

2009-01-21T17:51:00.001-08:00

So I think I mentioned earlier that I'm pretty sure I don't want to go into traditional biochemistry or structural biology because it's not exactly biology-meets-chemistry, it's kind of it's own thing. Here's excerpts from a PDF that I found on the UCSF website somewhere on one of their chemical biology pages:

Is there a problem?
Chemistry is a very mature science compared to biology.
Chemistry graduates continue to grow overall but at modest rates compared to biology graduates. What is making this happen?

...

What is Chemical Biology?
A paradigm shift in allowing scientists systematic access to chemical tools to probe important problems in biology.
It is not the same as biochemistry which uses chemical principles to probe biological molecules.
It is not the same as chemistry which is focused on synthesis and properties of small molecules.
It is not the same as molecular biology which modifies biomolecules to probe cells.

...

"It is different than molecular biology with the use of small molecules to probe biology offering numerous advantages to gene knockout and siRNA knock- downs, the modern tools used by molecular biologists. Proteins contain multiple functional sites and these"ablative tools" do not allow one to dissect individual functions. Moreover, cell signaling events occur quickly often with time-scales on the order of minutes. siRNA usually requires >24 hours to have its maximal effect and even then it usually only ablates 60-80% of the protein. Gene knockouts represent constitutive inactivation, unlike the acute inactivation that can be generated by a small molecule. Not surprisingly these different probes often generated different results. Small molecules represent rapid and dose-dependent probes of cellular function and the information that is generated is more relevant to drug discovery."

This is all very appealing to me. I'm all about small molecules and how they apply to biological systems. That, in my mind, is chemistry-meets-biology. I guess my main problem was that I read a lot of chemical biology papers that felt very...artificial. I think I describe it as "interdisciplinary for the sake of being interdisciplinary rather than having a point" somewhere on this blog, if not, if you know me in person those words definitely have come out of my mouth.

But I guess a lot of that has to do with the fact that trying to define chemical biology as a field is pretty new. I mean, the essence of what it is has been around for a long time called by different names. There has always been a chemistry-biology interface and medicinal chemistry has always been on it; this isn't exactly new. But defining this interface as a true discipline is, and trying to work more on the interplay between in vitro and in vivo with small molecules is definitely new.

I just need to find a corner of it that I feel like has a point and not, like, spend my life making aptamers that will never ever compete with real antibodies unless I find them to be extremely structurally interesting. Not that that is exactly a waste of time per say, just it doesn't seem satisfying to me. There's a lot of room to grow in this discipline, and I think interdisciplinary science is the way of the future.

Molecular imaging

2009-01-21T17:28:00.001-08:00

The article in PNAS about using magnetic resonance to visualize a virus (which I originally heard about from Derek Lowe's blog In the Pipeline) seems to hit everywhere. I saw it in Nature News, and even in the New York Times. If you look at the image side to side with the electron micrograph, the quality of the image is spectacular. There's even talk about the idea of single-cell MRIs not being too far out of the realm of possibilities in the next ten, twenty years. Wouldn't that be fantastic?

It makes me wonder if crystallography is going to become obsolete at some point in my lifetime. Getting proteins to crystallize is time consuming and difficult (not that I have ever done it!). Not all proteins crystallize and then there's the whole issue of whether the crystallized conformation is really even biologically relevant or whether the crystal is good enough to justify a model, etc. etc. If biophysical imaging techniques at the nanoscale keep getting better and better, who knows what we'll be able to do in structural biology. All that time and energy spent trying to crystallize a protein can be spent studying structure at a different level. It could even be like the boom in the complexity of synthetic organic chemistry and natural products synth after high resolution NMR became widely available.

Maybe being able to read NMR spectra all together will become obsolete and we'll just pull up 3D images of the compounds on the computer after making something in lab. Who knows.

The scientific world is going to be so fantastic by the time I get to really enter it.

Education

2009-01-21T16:55:00.001-08:00

There seems to be two camps of thinking about course decisions in my major. Biochem majors have a lot of requirements; it's the nature of being interdisciplinary. Some people in my major say "I'm probably going to grad school, I'm probably going to be thinking about science for the rest of my life and in a lab for the rest of my life, while I'm in undergrad I might as well take as much liberal arts stuff as I can." This seems legit, and this seems like where I thought I would be. After all, I'm the one who nearly didn't take gen chem my freshman year because I was ambivalent about the idea of studying science at a liberal arts school (and thought I was going to be just a biology major since I abhorred chemistry in high school). I get where that side's coming from.

But somehow, somewhere along the lines, I changed. I can't get enough science coursework. It's very strange. Every semester, there's another elective class that really want to take. Last semester I took advanced synthetic organic and a biochemistry seminar that fulfilled no graduation requirements. Next semester I'm taking advanced mechanistic organic, intro inorganic, and a biology seminar all of which do not fulfill any requirements. What is wrong with me? Am I becoming unbalanced?

And here's the thing: I love literature. I love music. I love history. I'd like to take some economics. I took a great religion class freshman year. I read novels and non-fiction unrelated to science voraciously during breaks. I like liberal arts classes, and there are any number of other things I am interested in beyond chemistry and biology.

So what changed? I guess part of it has to do with slogging through so much intro coursework to get here. Intro bio, intro chem, intro physics, even organic (as much as I liked it) was essentially an intro class. Now I am finally qualified to take small upper-level courses in my major with people who are serious about the subject matter, especially in elective courses. I know the professors and they know me, and it is all around a great experience usually. Seminars are great because they are more like journal clubs than classes. But you can't take those sorts of classes until you have the background.

The other thing is that I'm just do damn interested in everything. I seriously wish I could double chemistry & biology. It's the same side of me that wishes I could take everything under the sun that is not science that wants to take everything I can take in the two departments. Of courses, taking everything I would like to take is just simply impossible, but so it goes.

I'm also still discovering what exactly my scientific interests actually are. There's so much I just simply do not know, and the more I learn, the more I figure out what exactly it is that grabs me. For example, realizing that biochemistry is kind of it's own thing, and not exactly biology-meets-chemistry. Which is fine, great to learn about, and not what I want to do ultimately.

Sometimes I wonder, though, if I am jipping myself out of my last shot at taking liberal arts courses?

More on Watson

2009-01-20T16:19:00.000-08:00

Actually, I take some of that last post back. Tying in that old reference from Chargoff that everyone else had forgotten was pretty clever. Also, saying that Linus Pauling's three helix model was a bunch of BS took balls (I mean, seriously, he's Linus Pauling). I guess he did have several moments of important insight that took the biophysical and biochemical data to incorporate it into a coherent model. I guess I shouldn't necessarily undervalue the big picture thinking. (I think I tend to do that because I tend to see big picture more intuitively than little details, and I immediately assume that the little details are always undervalued because they are harder for me personally. I suppose there are other people who feel like it's the opposite.)

He also took back some of what he said about Rosalind Franklin:

Rosy showed Francis her data, and for the first time he was able to see how foolproof was her assertion that the sugar-phosphate backbone was on the outside of the molecule. Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.

Obviously affecting Rosy's transformation [in regards to the acceptance of the double helix model, which she had previously vehemently opposed] was her appreciation that our past hooting about model building represented a serious approach to science, not the easy resort of slackers who wanted to avoid the hard work necessitated by an honest scientific career. It also became apart that Rosy's difficulties with Maurice and Randall were connected with her understandable need for being an equal to the people she worked with. Son after her entry to the King's lab, she ad rebelled against its hierarchical character, taking offense because her first-rate crystallographic ability was not given formal recognition.

...Since my initial impressions of her, both scientific and personal (as recorded in early pages of this book) were often wrong, I want to say something of her achievements. The X-ray work she did at King's is increasingly regarded as superb. The sorting out of A forms and B forms, by itself, would have made her reputation; even better was her 1952 demonstration using Patterson superposition methods, that the phosphate group must be on the outside of the DNA molecule...

...we both [he and Crick] came to appreciate her great personal honesty and generosity, realizing years too late the struggles that the intelligent woman faces to be accepted by a scientific world which often regards women as mere diversions from serious thinking. Rosalind's exemplary courage and integrity where apparent to all, when, knowing she was mortally ill, she did not complain but continued working on a high level until a few weeks before her death.

Still a sexist (the woman had to prove herself to not only be competent, but first-rate, to be taken at all seriously), but the memoir was also meant to be told to reflect how they went through the process of figuring out the structure of the double helix, and those were his first impressions of her.

Interesting fellow, even if he is a raging bigot.

On Watson, Sexism, and Intellectual Laziness

2009-01-20T12:06:00.000-08:00

I'm reading James Watson's account of discovering the structure of DNA with Francis Crick in his memoir The Double Helix. Watson has always struck me as kind of a racist d-bag, and I know part of it is being a man of his times. But the sexism is also killing me, just in how he talks about Rosalind Franklin:

...Maurice, a beginner in X-ray diffraction work, wanted some professional help and hoped that Rosy, a trained crystallographer, could speed up his research. Rosy, however, did not see the situation this way. She claimed that she had been given DNA for her own problem and would not think of herself as Maurice's assistant.

I suspect that in the beginning Maurice hoped that Rosy would calm down. Yet mere inspection suggested she would not easily bend. By choice she did not emphasize her feminine qualities. Though her features were strong, she was not unattractive and might have been quite stunning had she ever taken even a mild interest in clothes. This she did not. There was never lipstick to contrast with her straight black hair, while at the age of thirty-one her dresses showed all the imagination of English blue-stocking adolescents. So it was quite easy to imagine her the product of an unsatisfied mother who unduly stressed the desirability of professional careers that could save bright girls from dull marriages to dull men...

Clearly Rosy had to go or be put in her place. The former was obviously preferable because, given her belligerent moods, it would be very difficult for Maurice to maintain a dominant position that would allow him to think unhindered about DNA. Not that at times he didn't see some reason for her complaints--King's had two combination rooms, one for me, the other for women, certainly a thing of the past. But he was not responsible and it was no pleasure to bear the cross for the added barb that the women's combination room had remained dingily pokey whereas money had been spent to make life agreeable for him and his friends when they had their morning coffee.

Unfortunately, Maurice could not see any decent way to give Rosy the boot. To start she had been given to think she had a position for several years. Also, there was no denying she had a good brain. If she could only keep her emotions under control, there would be a good chance she could really help him...

...The real problem-then, was Rosy. The thought could not be avoided that the best home for a feminist was in another person's lab.

...Naturally I was delighted when Maurice said I would be welcome at Rosy's talk. For the first time I had a real incentive to learn some crystallography: I did not want Rosy to speak over my head.

We have certainly come a long way, that's for sure in terms of women in the sciences. I know sexism still exists (especially in regards to getting a post-doc and tenure with respect to wanting to have a family), but thank god for scientists like Franklin who cleared the way for us today.

The other thing that bothers me about Watson is that he seems intellectually lazy. He describes himself as a "mathematically deficient biologist" and claims to have never taken any organic chemistry or advanced chemistry or physics in college at all:

My interest in DNA had grown out of a desire, first picked up while a senior in college, to learn what the gene was. Later, in graduate school, it was my hope that the gene might be solved without my learning any chemistry. This wish partially arose from laziness since as an undergraduate at the University of Chicago, I was principally interested in birds and managed to avoid taking any chemistry or physics courses which looked of even medium difficulty. Briefly, the Indiana biochemists encouraged me to learn organic chemistry, but after I used a Bunsen burner to warm up some benzene, I was relieved from further true chemistry. It was safer to turn out an uneducated Ph.D. than to risk another explosion.

He goes on and on about how Crick understood the math and theory behind crystallography, and how he only acquainted himself with it on descriptive terms because it bored him to learn anything about biophysics or biochemistry. He talks about how studying the metabolism of the bases is boring, and how basically all biochemistry and organic chemistry is boring unless it applies to the gene.

He makes a good point when he talks about Linus' Pauling's discovery of the alpha-helix, which Pauling did on descriptive terms before confirming it theoretically; that playing with modeling kits and pictures can be a useful way to understand structural biochemistry and biophysics. It's not inherently the fact that he relies on descriptive terms that bothers me. After all, I operate on a diagrammatic, descriptive level and am aware of the fact that I don't understand most of the math that the computer does for me. A professor that came to give a chem talk at Reed once made the good point that you don't need to understand hardcore physical and quantum chemistry to have a good chemical intuition about reactivity; for example, understanding steric hindrance, ring strain, and favorable conformations are all things we tend to do at a descriptive level, even if there are computational reasons to back up the chemical intuition. So some scientists are quantitative types and others are more qualitative types, and yeah, it takes all different types to solve problems in science, fine. It's just this total irreverence for the fact that other fields are interesting and worth learning about that gets to me. I hate intellectual laziness. It's one thing to be deficient in some areas in your background--no one knows everything. It's a completely different to not be intellectually curious enough to want to know more about things you don't know much about.

Watson doesn't really seem like a complete genius. He seems like a guy who was really really into this one pet issue and was determined and lucky enough to fall into a crowd of exciting and talented people (like Crick, Rosalind Franklin, and Linus Pauling) who actually were brilliant. It angers me that Watson can be such a bumfuck, and Rosalind Franklin can be off in the lab, being brilliant, giving herself cancer, only to be viewed as a tool for the boys to understand DNA. She made it her project because she wanted to understand the structure of DNA too, not because she was trying to be spiteful and difficult. They just assume that they can use her expertise and her intellectual contributions as if she is just technical support.

This book is fascinating from a history of science perspective because he writes in his unabashedly caddish way about it all. About the politics and personalities of these people you read about in textbooks. About a time when science was even more of an old boys club than it is now.

Also, maybe you don't need to be brilliant to be a Nobel laureate, you just need to be mildly creative and fall into a good in-crowd.

On Reading the Lit

2009-01-18T14:20:00.000-08:00

I don't read journal articles for fun the way I do for class--where I sit down and try to understand as much as I can, devoting hours to reading a single article. I read them just to be swept in awe by the overwhelming amount of fantastic science being done right now, browsing through, clicking around, mostly skimming abstracts and figures. Mostly I find myself reading biological chemistry and organic chemistry. And lately biophysics (mostly just the abstract and introduction because I really don't understand the math behind it). Some of the biophysical techniques that are going on...I can't even imagine how fantastic the scientific world is going to be in 10 or 20 years. For example, they can do NMR imaging of a virus now.

I read a review of total synthesis in the last hundred years and how far it has advanced. And docking carbohydrate synthesis on DNA as a way to functionalize microchips. And each leads to references to wander to, letting my mind wander and skim and wander and skim.

I'm realizing that it's now getting to be time to start actually keeping up with the lit--even if it is just skimming every few weeks, or even if it's just reading C&E News and/or review journals. Since there's so much out there and no one can read everything, my professors are reading the same journals, they've just been doing it for longer and with more specialized interests.

I finally have the background to get a vague sense of what articles in the current lit (at least in organic chemistry, biological chemistry, some of the more qualitative aspects of biophysics, biochemistry, and cellular & molecular biology) are about, even if I don't fully understand them, and learning about science isn't going to be spoon-fed to me through assignments for the rest of my life. It's time to start getting into the habit of reading journals like it's time to get in the habit of reading the newspaper. Not cover to cover, not necessarily every day (or even every week--after all, I still am a student), but as something I do periodically.

On Stupidity

2009-01-15T13:06:00.000-08:00

My roommate's thesis advisor sent her a link to the following article The Importance of Stupidity in Scientific Research. It was interesting to read, because I think it is absolutely true.

Second, we don't do a good enough job of teaching our studentshow to be productively stupid – that is, if we don't feelstupid it means we're not really trying. I'm not talking about`relative stupidity', in which the other students in the classactually read the material, think about it and ace the exam,whereas you don't. I'm also not talking about bright peoplewho might be working in areas that don't match their talents.Science involves confronting our `absolute stupidity'. Thatkind of stupidity is an existential fact, inherent in our effortsto push our way into the unknown. Preliminary and thesis examshave the right idea when the faculty committee pushes untilthe student starts getting the answers wrong or gives up andsays, `I don't know'. The point of the exam isn't to see ifthe student gets all the answers right. If they do, it's thefaculty who failed the exam. The point is to identify the student'sweaknesses, partly to see where they need to invest some effortand partly to see whether the student's knowledge fails at asufficiently high level that they are ready to take on a researchproject.

Productive stupidity means being ignorant by choice. Focusingon important questions puts us in the awkward position of beingignorant. One of the beautiful things about science is thatit allows us to bumble along, getting it wrong time after time,and feel perfectly fine as long as we learn something each time.No doubt, this can be difficult for students who are accustomedto getting the answers right. No doubt, reasonable levels ofconfidence and emotional resilience help, but I think scientificeducation might do more to ease what is a very big transition:from learning what other people once discovered to making yourown discoveries. The more comfortable we become with being stupid,the deeper we will wade into the unknown and the more likelywe are to make big discoveries.

I think Reed is actually abnormally good at making you feel very small and very stupid. Even if it's not quite the same as research, the classes are geared towards giving you problems in the current literature and making you think about them in novel ways. My organic chemistry tests and biochemistry tests were not dependent on just knowing the information, but also knowing the information and learning how to apply it to a new setting. We also spend a lot of time sifting through the literature in upper level classes, and you get a sense that you are very small and there is a whole unknown, unsolved world out there. On top of which, we have an unusual grading policy where we are not shown letter grades for the work we do; we are assigned letter grades for our classes, but to see them we have to ask our advisor, and we are only informed if we performed above a C which is "satisfactory" when we receive reports at the end of the semester. You see numbers, you see correct or incorrect answers on exams, you get comments on written assignments, but you never know exactly how well or poorly you did, just an overall sense, which is often skewed anyway. I also struggled with my intros, and didn't really start to do well until I hit my upper level classes, so I dealt with a lot of academic failure and feeling stupid in my time. And even so; it didn't end there. In advanced synth a class I did very well in, Pat assigned us problems that he didn't even expect us to get correct. I mean, sometimes I did but mostly I didn't. The point was learning a process of solving problems and to demonstrate that you have picked up that process. The point was just to grapple through some really tricky questions that are a little bit above your current level.

The school also pushes you to your limit emotionally; I feel intellectually accountable for my work, and like when I'm not doing it well I'm actually disappointing my professors. Basically, Reed College makes me feel very stupid, even when I'm doing well. I feel like there's always more I could be doing, more I could be learning, more about every topic I should know. This is not quite the same as addressing new, unknown problems (hell, the known ones are intimidating enough), but the feeling that I'm stupid is something I am very used to, and embrace. I've even heard the phrase "if you don't feel stupid all the time at Reed, you're not doing it right".

The world is a big place with a lot of smart people in it. No, I'm not a super genius, and in some ways I'm not even that conventionally intelligent (I have trouble with things like standardized exams). I don't mind the idea of failure in lab, because so many things are out of your control. Isn't that the exciting part, muddling through until you figure it out? Tweaking this and that? Few things are as simple as they look on paper. Lab is different from school, which is awesome in my book. It's a whole different set of puzzles. But I like chance games and gambling. Things that involve a lot of skill and a lot of luck. Keeps things exciting.

So what is the big deal about feeling stupid all the time anyway?

Life plans

2009-01-07T21:32:00.001-08:00

I've been thinking more and more about graduate school lately, and I'm pretty into the idea of going. I've spent a lot of time not marrying myself to the idea due to a lot of reasons (mostly including self-doubt, a low GPA, a keen awareness of how competitive the world is, and a certain resistance to the idea of doing something just because it's what you are "supposed" to do) and trying to convince myself it's not what I necessarily want, or that I shouldn't close myself off to other options in life or to the idea of not doing it. But when it comes down to it, I want to do science at that level eventually and I know that, and have basically been becoming more and more sure that I love science, I can handle being pushed to my limits with work emotionally, and that I have the drive to work on the sort of project a PhD would be. And while I'm not the best test taker, I have strong skills in other areas. I'm good in the lab, I'm good at communicating ideas face-to-face, I know how to retrieve I don't know quickly on the internet, I can talk about science cogently, I know how to digest the primary lit. I know professors who can attest to these skills.

But then I try to take things in perspective. I'm studying the hard sciences at a hard school. I know several profs who could write me good recommendations. I have a lot of research experience. And a really broad scientific background with a solid academic program. These things all matter too, right? Perhaps matter more than my GPA?

I don't know. It's hard not to worry, but I spend so much time consoling other people that I'm starting to believe my consolations. It is scary. We have this giant recession and everything worth doing, or so it seems, is incredibly competitive. Medicine and law and grad school in most other fields are more competitive, it seems, so maybe I should count my blessings.

But off of this "woe is me, can I hack it?" shit, I think I've finally figured out what I want to study, broadly. Basically, synthetic organic heavy-yet-still-interdisciplinary chemical biology. I want to do something more at the interface of chemistry and biology. The ideal program would be something like (ha! ha! ha! after talking about all this GPA woe) UCSF's Chemistry & Chemical Biology program. As far as I can tell, a lot of this interdisciplinary stuff is under all different labels, so my actual PhD could be in any number of things (including biophysics), it all depends on the individual labs I am interested in. I should start keeping lists of labs that are publishing projects I'm interested in that I come across in the lit.

So this is the plan right now: finish off this year (my junior year) strong, get a another summer of research this next summer (and prep for the GREs), take the GREs next year, then take a year off and apply to grad school during that year, and tech. I've also seriously thought about moving to the Bay Area after Reed, although possibly staying around Portland and trying to get a job at OHSU.

Okay, this moving to the Bay area thing is a recent idea, related to this whole actually I kind of want to go to grad school thing. I visited some friends there who were in biophysics programs at UCSF and Berkeley. Which basically was what made me come to believe that these were the sort of people I wanted to be around and the sort of environment I wanted to be in. We talked about science! Even when we were in the bar! And more science! Some people think this is sad and indicative of an utter lack of ability to fit in socially. Perhaps, but I want to be able to talk about science with my buddies when drunk. The facilities at UCSF blew me away, and the projects they were doing where just so spectacular. The sort of stuff you read about in Nature, but at a small liberal arts school, we just don't even have close to the facilities to do.

But oh yes, I was talking about why I want to move to the Bay after Reed. It's a bigger city than Portland, but one I have ties to. A lot of people I go to school with grew up there, but there are also a lot of Reed alumni who move there for work or grad school, and so there's the sort of safety net of being around Reedies, but the novelty of being in a new city. In addition, I was born there and lived there until I was 2 and a half, and my parents have a lot of family friends who live there, some of their oldest friends from before they were married. There are even a couple friends from high school who went to school out there who might be around. It's not totally restablishing myself in a new city as much as moving other places would be.

Also, as far as I can tell, The Bay area and Boston are the place to be for the biological sciences. There's just such a neat relationship between the academic powerhouses and the biotech industry in those locations that I don't think exists to the same degree elsewhere. I could probably find a job as a tech, people seem to, at least. So at least I could be connected to the science, because I think I would be really unhappy in a situation where I wouldn't be doing science to some degree. Also, San Francisco rocks! The city is gorgeous, the climate is great, there's plenty of hipster culture and coffee snobbery and all that stuff. It's still the Pacific Northwest, which I love. I love the West Coast, and I don't really want to move back to the Midwest or East Coast. It's just a vibes and personality mesh thing. The only concern is that it's expensive to live there and rent is expensive. On the other hand, it's just for a year, maybe 2; I just need to sustain myself, and I'm not looking to save money. I can live reasonably cheaply, and I don't want to live in someplace boring just because it's cheap to live there.

I love Portland. Portland is a neat place to live, and I only got tastes of what it is like to be a person in Portland and not a student who spends her whole life between the library and lab during the school year, but I spent a summer there and got a feel for it, and I really do like the city a lot. It's been good, but after 4 years it's time to see more of the world. The argument to stay in Portland is that I really do have a lot of friends out there and possible employment prospects. It's sort of a comfort zone thing. Also, it's really cheap to live in Portland, and Portland is far from boring, unlike a lot of other cheap places to live. Portland is a great place to be a 20something.

So anyway, that's my current life plan. Finish undergrad, take a year off in the Bay Area, go for the PhD. Narrowing down what exactly I mean by "synthetic organic heavy chemical biology" might be good too. Figuring out if those projects are in Chemistry & Chemical Biology programs, Chemistry programs, Biochemistry programs, Pharmacology programs...

What comes after the PhD? Academia, I think, although industry and a number of other paths aren't out of the picture either. This is a little more hazy. But seriously, I think academia is more my style. My friend and I have a running joke that if we decide in ~10 years and/or during our post-docs that if we're not feeling the academic route, then we're starting up a biotech company together; he thinks there's a 10% chance of that happening. So maybe it's making the big bucks in biotech. In any case, it's something, although I'm not quite sure what.

PLoS journals

2008-11-30T15:32:00.000-08:00

Constance Bailey: http://www.nature.com/nature/journal/v441/n7096/full/441914a.html
Constance Bailey: (sorry, I've been really intregued by the PLoS journals lately)
gvtennis55: hahaha
gvtennis55: i like the title of this article
gvtennis55: 14.7 is legit, dude (14.7 is the impact factor of PLoS biology)
Constance Bailey: http://www.nature.com/nature/journal/v425/n6958/full/425554a.html
Constance Bailey: yeah
Constance Bailey: i mean, it seems to have legit science
Constance Bailey: and so forth
Constance Bailey: just it's running itself bankrupt
gvtennis55: dude that would suck if you published in this journal
gvtennis55: and then they were no more
gvtennis55: IF of zero motherfuckers!
gvtennis55: also, what's up with this nature article about how it's competitor will ultimately fail with their competing business model?
gvtennis55: because if nature can convince enough authors that this PloS won't be around, nobody will submit and the prophecy will come true
Constance Bailey: it's like the NPR/PBS of science journals
Constance Bailey: i like it
gvtennis55: i know yo udo
gvtennis55: (you also like NPR)
Constance Bailey: they should do pledge drives
Constance Bailey: take the NPR business model
gvtennis55: hahahahaha
gvtennis55: you mean embrace what this article says they should run from - a permanent reliance on philanthropy?
Constance Bailey: "donate 100 dollars to PLoS and we will give you this limited time PLoS logo 1,000 mL micropipette"

2008-11-29T18:38:00.000-08:00

AHHHHHHHH. The end of the semester. It's hectic. Writing a bunch of papers, final lab reports, have my final exams coming around the corner. So much work left to do for my synth final--I need to write a paper and then be prepared for an oral grilling.

I'm midway through a paper on inducible nitric oxide synthase's role in type 1 diabetes, got a decent chunk of that done, and but have worrisomely little done on my synth paper on the total synthesis of pyranicin. Oh, and there's labwork to be done and so on and so forth...rawr. it'll be tough for the next few weeks.

But in more exciting news:
--there's a good chance that I'm going to Germany this summer to do biological chemistry work on a polyketide biosynthetic pathway.
--I may get to do a not-for-credit hang out in the lab and work on a project type independent study thing with my favorite prof (the one I worked for last summer who does the synthesis of OncoTools, or carboxyllic acids with pH switches to give them a pKa ~6.5 to target the acidic regions of small tumors that can be tagged with radioactive halogens...at least in concept...we haven't made enough of one to put it into practice, but yeah organic synthesis how I love thee).

2008-11-21T18:38:00.000-08:00

I'm having a big dilemma over what courses I should take next semester. We are on a unit system (as opposed to a credit hours system), and a normal load is 4 units, although you can take 3.0-4.5 units without underloading or overloading.

Next semester I was originally signed up for:
--intro inorganic chemistry (1.0 units)
--statistical thermodynamics 1.0 units)
--metabolic biochemistry (0.5 units)
--biochemical methods (0.5 units)
--Johannes Sebastian Bach (1.0 units)

Bach is a musicology class to fulfill a distribution requirement with a professor I rather like, so it should be fun. This adds up to 4 units; a pretty normal schedule.

Well then I decided I didn't feel like taking i-chem lab. As a biochem major, it's not required. (I majoring in biochemistry & molecular biology, but at another school that had minors, I would probably be close to doing a minor in chemistry). In any case, I'm a little burnt out on lab classes. I love being in the lab doing research, but class labs are different. Everything isn't where you need it to be, they're short and hectic, and you can't do extended experiments because science doesn't work in once a week four block chunks. It's nice to be exposed to some lab techniques, but in reality I pick those up faster by doing research in a given field, and I'm kind of at a point where I understand generally how labs go and I'm not getting that much out of taking them anymore. Beyond biochem methods and analytical chemistry, both of which I need to graduate, I really don't intend on taking any more lab classes. Also next semester, then, will be the first time in college that I will only be taking one lab class (I'll probably still TA for organic, but whatever).

So the ramification of dropping inorganic lab is that I am taking 3.5 units. Still not technically an underload, but I started fishing around for half unit classes. This is dangerous, because in the sciences half units are classes that don't have lab components (it is pointed out frequently that all humanities classes meet with only a lecture component and you receive a full unit).

My first thought was a membrane-membrane interactions seminar. It's a 4oo level bio class where you meet for two hours a week to talk about molecular neuroscience papers. Seminars are pretty low key, generally, besides that one day when you have to stand up in front of ten or however many people are in the class and talk about a subject for an hour with our professor grilling you (and boy, does that prof know how to grill, he's a toughie). Otherwise, pretty mellow.

My second thought was advanced mechanistic organic chemistry. This might be a bit more work, but maybe not. It meets for three hours a week, and it's lecture only, so problem sets, articles to read. It's about MO theory in organic chemistry and it goes over the theory behind all those weird-ass concerted ring closings which would be nice to know about, even if my interests are ultimately more synthetically oriented (Woodward Hoffman rules, etc.) There's a lot of computer modelling. Also a small class, probably also mellow. With a number of my study buddies. It also may not be offered next year, whereas the biology seminar most definitely will.

My main fear is that if I take inorganic, advanced mechanistic organic, stat therm, metabolic, biochem methods, and a humanities class, I'm going to be drowning in work all the time even if it isn't technically an overload (I also might just maybe hate chemistry after taking all that at once...and will be taking no biology classes that semester). Especially since I am far from a p-chem-minded type and stat therm is going to be fucking hard for me. On the other hand I can always drop something (most likely advanced mechanistic or my humanities class) and I really shouldn't be afraid to do that. So, should I go for it, or is that crazy?

In other news, I am most likely going to doing labwork in Germany this summer in a chemical biology/biomolecular chemistry lab. More on that later.

2008-11-14T21:09:00.000-08:00

I'm taking a topics in biochemistry seminar course where we read two papers a week. The topic the course covers this year is chemical biology.

Now, I'm someone who loves organic synthesis, who loves biochemistry, and who loves molecular biology. I think my mind is set up for the type of conceptual trouble shooting of organic chemistry on terms of diagrammatic reasoning as opposed to mathematical reasoning (like in a lot of computational and biophysical approaches). At the same time I'm an arrow pusher, and I think of this very much at a structural/chemical intuition level as opposed to a gross biological scale. But as much as I love organic chemistry I like applied organic chemistry. The entire complexity of biochemical systems is both fascinating and overwhelming. So where this rant is all going, is basically I thought chemical biology would be exactly my cup of tea.

Turns out that there are a lot of chemical biology projects that seem just sort of...pointless to me. Like they are doing an interdisciplinary project for the sake of being interdisciplinary? I'm skeptical, because a lot of these projects don't seem to be tackling interesting questions, really. I mean, there is some chemistry in there that appeals to me, some biology, but rarely do I find a paper where I think "yes, this is a good mix of concepts."

But I think, actually, I'm probably going to end up in a chemical biology program, it'll just be a matter of finding one of them that does something really cool, or the intellectual challenge of working on a piece of a collaborative project knowing the big picture but being an expert in a small area. Or somesuch.

Trials and Tribulations of undergrad projects

2008-10-30T15:16:00.000-07:00

So at Reed we do independent projects in biology classes. They're usually kind of fun, and it's kind of a unique part of the curriculum here. However they get annoying for the following reasons:

1) we have 6 weeks to do them, so we are discouraged from doing time consuming or complicated techniques (because you just can't)
2) We aren't allowed to do something expensive. If we need to buy something expensive (like, say, a $300 antibody), we better damn have a reason for purchasing it, like someone else in the department will use it later. It can't just be your pet antibody for your pet protein. We used to have the resources to write a grant for expensive materials for independent projects, but one of our big teaching grants has run its course, so the department is tighter on cash than it has been for a while.

This makes sense; we're a small liberal arts school with limited resources. Our science program is solid, but as a small liberal arts school we don't have a lot of fancy schmancy equipment nor do we have a large budget. The opportunity to do independent projects is great for gaining lab experience, and a great opportunity, but at the same time, more of the money is spent on the faculty's research and people's undergrad theses. As it should be.

Depending on the class there is more or less guidance. Animal Physiology, Bio 381, happens to be a junior/senior class. Thus, there is little guidance at all and we are encouraged to think like scientists and figure out our own problems based on issues we are interested in. Good, great, I'm liking that. But it's hard because...shit son, it's hard enough to find an experiment that hasn't been done before, period. Add that on to a no more than 30 dollar budget and a 4-6 week time scale, and you have really slim pickings.

So we searched and searched and found this interesting pro-apoptotic signalling molecule, ceramide. It's kind of neat because it's a structural membrane lipid as well as being a pro-apoptotic signalling molecule, which is unusual. An experiment in the past showed elevated amounts of ceramide in the prescence of ionizing radiation (well in this case gamma radiation), in similar fashion to the way it was elevated in the prescence of TNF alpha (tumor necrosis factor) and chemotherapeutic drugs. Well, Reed has a nuclear reactor, kind of one of those odd little anomolous things--I'm actually a licensed operator, it's nearly completely run by undergrads--so it seemed like a good resource to take advantage of. Why not repeat the experiment looking for ceramide levels, but look for it with a greater variety of types of ionizing radiation (neutrons, gammas, and betas) in the reactor? Well cool.

Except then the issue of how to quantify the ceramide comes up. There's a kit that uses a radioactive phosphorous and a kinase, but that kit is expensive. No dice. Using a HPLC is probably the easiest method, but to my knowledge, both the HPLC in Arch's phyisology lab and the HPLC in the organic/biochem reasearch labs are not up and running. Okay. Oh here's a method, you can 1) extract the lipids out of the cells 2) run some silica gel chromotography (we found an elution plan in the lit) 3) functionalize it with benzyl chloride 4) do absorbance studies. Oh wait, forget that silica gel chromotography is a pain in the butt, that would take a shit ton of cells, we'd need to check to see if we actually purified it with the GC-MS/NMR, and...well....that's not exactly happening in 6 weeks on top of coursework. Okay, nix that.

Well, it turns out that a molecule in that pathway, spingomyelin (well, it's actually made from spingosine, but it's in the same pathway) turns into ceramide. So it would just be easier to take a look at upregulation or downregulation of the spingomylenase. We found a paper (which I don't have on hand and am too lazy to look up) about how TNF alpha and chemotherapeutic drugs lead to an upregulation of singomylenase, just as they lead to elevated levels of ceramide. BUT, no experiment was done with ionizing radiation. So, bingo. Primers are cheap. These are even published, so we don't have to worry about our primers not working (even if primer 3 input has done me well in life for designing primers for arbitrary genes, it's always nice to be assured that they have worked in the past).

Okay, problem. We asked if we could culture some fibroblasts to do the experiment. And got a "no, it's too complicated to do in 6 weeks". But I mean, if we take arbitrary dead tissue, that's confounding the experiment. Ischemia causes apoptosis and we're studying apoptosis! Not cool. I mean I see what he's saying, but damn. He suggested looking into using, say, sheep's blood. That shit is cheap. He also said using qPCR was unnecessary. Well, everyone uses qPCR now. Band brightness is a shitty way of determining upregulation vs. downregulation. I mean, I know that the qPCR machine is in heavy use by people doing their theses and the cytogreen dye is expensive, but it's really hard to make any sort of real interpretation of anything by band brightness and no one really does it anymore.

So here we are. We tried to come up with a cheap, fisable experiment and got shut down. All due to culturing a few fibroblasts. Maybe we can still do this experiment with sheep's blood? Or maybe the cell bio prof has a few extra cell lines floating around her incubators?

In a similar fashion, anyone who wants to do a Western Blot pretty much, well, can't unless they are studying a protein that other people in the department are studying.

This shit is hard.

2008-10-16T15:13:00.000-07:00

I was talking to a friend who worked at Amagen this summer, and she told me that basically the people she was working with were saying that organic chemistry is a dying field--at least as to its usefulness in industry, and that small molecule drugs are pretty inefficient when comparing the cost of developing them to the coast of drugs developed with biochemical methods.

Which leads me to wonder, I guess. I came to college gun-ho about doing biology. Then freshman year I discovered that I really liked chemistry. So I decided to do the biochemistry & molecular biology major. Then sophomore year I fell in love with organic, and now I find myself more drawn to skimming websites like Totally Synthetic than reading about biology or biochemistry, and structural biology is interesting, but most interesting when you put funky artificial bases and peptides in there. My advanced synthetic class is my favorite class I have ever taken. So here I am, in some place, falling more and more in love with a "mature and dying field," as someone once put it? I guess as an academic there will always be room for synthetic chemists, but there's something really appealing about the idea of doing drug design. I mean, I still love detailed cellular mechanisms, and my animal physiology class is great. Molecular biology picks questions that I guess I find really interesting. Mostly, though, what I like about synthesis vs. molecular biology or biochem is that you are making things instead of breaking them apart to see how they work. It's a whole different set of problem solving.

I think I might take the GRE chemistry subject test next year, though instead of the biochem/ mol. bio one because I really do think I want to go to some sort of chemistry grad school. But I almost definitely don't want to go to grad school right after undergrad. The world after this year is so incredibly uncertain. I don't even know what discipline I want to do my senior thesis in.

RSS feeds

2008-10-15T17:20:00.000-07:00

So instead of doing anything productive today, like studying for/finishing my midterms, I decided to add several journals to my google reader in hopes that RSS feeds will ~~provide me with more procrastination opportunities~~ inspire me to keep up with the lit. The problem means diverse interests=lots of journals I could (attempt to sort of) keep up with. Right now I have RSS feeds for Nature, Science, JACS, JOC, JBC, JMB, PNAS, Journal of Med. Chem., Angewandte Chemie, Biochemistry, Bioorganic Chemistry and Organic Letters. Which is pretty much everything on my list except Cell, Tetrahedron, and Synthesis, which I can't find an RSS feed for on google reader. Oh I guess I could add Chemistry & Biology and a few more, but anyway this list is getting unmanageable. I was surprised to not find Cell, but it seems that synthetic chemists are bigger RSS feed users than biologists because I found more obscure chemistry journals than obscure biology journals with feeds set up.

Regardless, we'll see if I actually skim through the lit now, or if it just piles up as more unread stuff on my google reader.

In class today

2008-10-15T01:04:00.001-07:00

Andrew (a classmate): (starts to explain how an assay works) Well then it activates the MAP kinase pathway.
Arthur (prof who teaches structural biochemistry, whose degrees are in chemistry): Oh no!
Andrew: Which is just a lot of blah blah blah.

haha, yes.

What are men good for anyway?

2008-10-14T12:46:00.000-07:00

"Males are kind of like pasteur pipettes from an evolutionary point of view. You need something to drop the reagent and when you're done, you can dispose of the receptacle."

This was my animal physiology professor's take on the fact that males are conceived in higher number than females, but also have a higher rate of post-natal death.

2008-10-13T23:49:00.000-07:00

Castro (or is it Songashira? I recall reading something about the name of the reaction depending what the leaving group was and whether the thing attached to it was aryl or alkenyl or somesuch) couplings showing up in my biochem reading about flourescent RNA?

I love when my classes synergize.

this week is a bit of an academic hell week. I'm part way through a take home advanced synth test; gotta finish that up and finish studying for/take a take home animal physiology test, then finish studying for and take a biochemistry test. On top of that I'm sick.

Dog Genetics & SN2 transition states

2008-10-11T10:31:00.000-07:00

Yesterday I went to a talk by one of the NIH Cancer Genetics Cheif, and part of the NIH Human Genome Research, that was about....dog genetics. I mean, they tied in medical applicability to Dwarfism (lessened IGF serum levels in all types of small dogs resulting in not allowing their growth plates to expand, and a either a lower copy number of that gene or a high copy number of a gene that repressed it, I can't remember), but mostly the grad students and post docs had their own little pet projects that they were studying because they found it interesting. Like, for example, someone had a wire-haired Dachshund and did their PhD thesis on studying the gene for wire-hair. They study hair type, body type, bone structure, back arch, and a little bit of behavioral stuff in this group. When you ask the lady why they choose projects in the lab she responds "we find projects that we think are interesting."

The science--in terms of the method--was very solid and well presented at a level that was comprehensible to students with little background, but was still engaging to the profs, but I felt the whole time that the topic of dog genetics was...a little goofy? Especially the motives for the projects "why does my corgi have short legs?" or "why does my dachshund have this type of coat" which seems strange that this would be my gut reaction. I mean, I think that, since biological systems are so interconnected, approaching all sorts of questions can be useful to our greater knowledge regardless of what the direct application is, and it's never a bad thing to know more about the world. I just found it interesting that she managed to swing NIH funding for studying these little pet areas of the dog genome (excuse me for the pun). She even had a project called project PyDo (for "phylogeny dog").

And to an unrelated topic, I really like tutoring because it keeps me learning new things all the time. Like, for example, that the SN2 transition state is chiral despite being Sp2. Having five things around it makes it non-superimposible even if the three substituents attached to carbon are planar (and the nucleophile and leaving group are hanging out in the p-orbital). There is a different teacher from who I had and a different book first semester, and the teacher is really into theoretical organic (i.e. the teacher I had would never ask what the hybridization of the transition state was), so the emphasis is totally different, and it's kind of like getting a new perspective on the subject as well as a refresher to help people.

2008-10-09T20:08:00.000-07:00

Today I heard a chem talk given by a computational organic chemist Jim Duncan, a prof from our neighboring liberal arts school, Lewis and Clark, who publishes research (has a few in the Journal of Organic Chemistry) on concerted cyclizations and rearrangements. Much of it was well over my head, as I don't have the greatest grounding in theoretical organic chemistry (I mean, I learned Diels-Alder in sophomore organic...yup, that's about it). I know nothing about the Woodward-Hoffman Rules or Frontier Orbital Theory save that they exist, and most of my organic training thus far has been thoroughly grounded in synthesis where it's okay to hand-waive mechanisms to a degree, because what really matters is what the end result is. Pat, the prof who I took organic II, worked for over the summer, and am taking adv. synth from now, like most synthetic chemists, sees mechanisms largely as a tool to evaluate reactivity. He stresses mechanisms--in fact, most of our problem sets are figuring out mechanisms of named reactions that are analogs to simpler reactions we already know but the course is...well...aimed at preparing us to be able to pick up a synthetic paper and be able to read it. It's kind of mind-boggling to me that there are people whose entire carriers are devoted to performing very complicated calculations on the computer about chemistry to determine the mechanistic basis for how reactions work at an orbital level. One of my other professors does this (although he still takes thesis students who do wet work in synthesis as well), and I may eventually take that class (adv. mechanistic organic) depending on how things pan out next year. Well, we'll see. It's something I'd like to know more about, might enjoy taking a class in, but at the end of the day am glad someone else has a passion for it.

Incorperation of Bioenzymatic Synthesis in Total Synthesis of Natural Products

2008-10-09T13:12:00.000-07:00

So I think I've found an area of biological chemistry that really really interests me: using enzymes in total synthesis. It seems to be a relatively new tool to pull out of the bag of synthetic tricks, but I have found papers that use a combo of bioenzymatic snytheses and traditional synthetic organic reactions (in this case, a Stille coupling), as well as a total enzymatic synthesis of this particular set of bacterial products that seem to slow down tumor formation. I'm going to write a paper for biochem about this (focusing on the biochem side instead of the synthetic side...i.e. the relevance of products and why this particular enzymatic transformation is synthetically useful as opposed to the synthetic methodology aspect...but both catch my interest). But it's really handy because enzymes do all sorts of crazy shit that we don't do well...like stereochemical control and massively concerted reactions...and additionally are pretty green (i.e. don't require large amounts of heavy metals that are a bitch to dispose of). They can only be used for very specialized transformations, so there's a lot of work that still needs to be done in this field. Also, they can be a bit of a bitch to purify, but then again, organic reactions in general can be a bitch to purify.

This seems like an area that satisfies the synthetic chemist and the biochemist in me.

decarboxyllating on the rotovap?

2008-10-08T21:08:00.000-07:00

In the adv. synth. lab, there are dry ice rotovaps. They're pretty efficient and nice, but there are only two of them and there are eight or so of us. So sometimes we set rotovaps up in the regular o-chem lab (which is right next door, and they are conjoined by a weighing/reagents room) which are normal, cold water rotovaps and aren't nearly as efficient. I was trying to some last traces of ethyl acetate and ethanol out by rotovapping out some toluene, and I really had to crank the heat on one of the rotovaps in the regular o-chem lab in order to get such high boiling solvents out (whereas it would have been no problem with one of the dry ice rotovaps). My professor comes by and he says "well, I guess you have to really crank the heat on that thing to get toluene out. Now, normally that would be a problem, but we're just going to decarboxyllate that diacid anyway by refluxing in toluene for 48 hrs, so if some of it reacts in the rotovap, that's fine." ( It's funny--if I had heard a sentence like that a year ago it would have zero meaning to me.)

It's always nice when lab inconviences work in your favor.

I also really miss my old research lab (which is upstairs). Where there were only two of us, and glassware was plentiful and the only person I needed to share the rotovap with was my labmate.

What is the point of chemical biology?

2008-10-08T16:43:00.000-07:00

I am taking a seminar course on chemical biology. Well, it's actually "topics in biochemistry", but every year there is a theme, and this year the theme is chemical biology. We read a couple papers a week and discuss them.

Which leads me to ask--what is the point of chemical biology anyway? All these papers we're reading--especially the ones that self-identify as chemical biology (like Nature Chemical Biology), seem to have these extremely interdisciplinary projects for the sake of...having an extremely interdisciplinary project? A lot of the issues addressed are issues we already have pretty good solutions to (for example, we have a lot of methods for tagging cells and proteins. not that more methods aren't great...but not more methods that have no shot at being as efficient as the ones we already have but are just structurally interesting seem kind of pointless).

The problem I'm finding, is that my interests in different subjects are for different reasons. I like the questions that are posed by molecular biology, and the idea that there are concrete ways to approach these questions in a methodical fashion. What draws me to organic synthesis is the intellectual puzzle of it, as well as that I like to make things (I like making things much more than breaking them apart, which is what you do in biology, but that's another rant). What I like about structural biology that there is a combination of elegance and totally overwhelming complexity in proteins and other biological structures. So, you might say--what if you mash all three together? Shouldn't that be exactly your cup of tea, Connie?

No, not really. The questions posed by chemical biology are boring to me, and the synthesis are buried in the supplemental information if discussed at all. What it basically amounts to, as far as I can tell, is science that is unsatisfying to the molecular biologist and the synthetic chemist in me. And what I do like about it are not the ideas explored and the overall concepts of the papers (well, one was about lipid membrane evolution, and chemical evolution studies are actually pretty cool), but little snippets of sections that were probably done by specialists. Oh, that was a neat series of reactions for the synthesis of n-substituted glycine peptide analogs. Oh that was a cool way to stabilize that protein domain. Oh that's cool that you can stabilize an alpha helix by stapling the end with a Grubbs catalyst.

I mean, isn't it obvious that we are in an interdisciplinary age? Most biomedical labs in particular have an incredible amount of collaboration between specialists. I mean, synthetic organic chemists (supposedly) primarily synthesize compounds with biological relevance (unless they're doing materials science); biology relies on chemical techniques (protein assays, affinity column chromatography, MALDI-TOF MS, etc. etc.). Crystal structures being solved of receptors as well as genetic studies help computational chemists design drugs for the synthetic chemists to make which need to be tested in animals before being put on the market. So what is the point of going out of your way to say "hey! look! look! it's chemical biology! it's chemistry and biology! things are interdisciplinary!" when it's all kind of a natural process anyway? What ends up, as far as I can tell, are a bunch of projects that take really ass-around-your-elbow approaches to problems for the sake of mixing the diciplines, which just seems kind of pointless to me.

Please enlighten me, though, if you think I'm being closed-minded and if there's something I just don't get.

what can I say; I'm a sucker for bad science puns.

2008-10-08T09:53:00.000-07:00

So, the guys who discovered Green Flourecent Protein just won the nobel prize. I was reading a blog post commenting on this, and one of the comments was the following:

"Hmm... Chemists FRET about the trend in biological Chemistry Prizes?"

Incidentally, I just explained what GFP was to someone last night...

randomness about departments

2008-10-07T12:09:00.001-07:00

This is more a comment on departmental politics at Reed than anything particularly related to science, but.

Today I received an email from one of my profs asking if I could go to lunch with the seminar speaker. This is the third email of the sort I've gotten this semester, and I know several people who don't get them at all. When I looked at who it was sent to, it looked basically like my prof thought "hmm, it's an organic talk, who is into organic?" "I know, Melissa, Jess, Todd, Ian, Connie, Gildevin...yes they all like organic chemistry. Okay, yeah, I guess I'll email them." In the chemistry department, it seems like it's usually a random list of who a prof thinks would be interested, or a list sent out to their 300 level class and thesis students. In the biology department, though, if you are a declared biology or bmb major, you get an email every week about what the lecture topic is going to be and asking if you want to go to lunch with the speaker. Several of my friends have asked how to get on the mailing list for chemistry talks, and the truth is there is no mailing list.

In the chemistry department, in similar fashion, someone (usually Randy, the stockroom manager, or John Witte, a staff member who is an NMR wizard) goes to Trader Joes and gets milk and cookies. The bio department caters cookies and coffee. Then at the end of the year picnic, again, chemistry just goes to Cosco and buys some burgers and then Randy pulls out a rusty old grill, whereas biology is catered.

I guess at a larger school 25 or so majors wouldn't seem like a lot, but biology is one of the larger departments at this school, whereas the chemistry department has 10 majors in my year and 7 faculty members (that isn't counting people like me, so I guess bmb majors factor in as well in both departments), one of the best faculty to student ratios at the school. Also interesting is that, because there is no particular sequential order that you are supposed to take bio classes in (other than classes that are tend to be sophomore/junior vs. junior/senior), basically sophomore year you are taking 300 levels, whereas in chem sophomore year you're just taking o-chem first semester, so you're not in upper levels yet. There are way fewer sophomores that go to chem talks than sophomores that go to bio talks (ratio wise, because fewer students go to chem talks in general), meaning that I feel often like at a personal level, the department feels smaller because you aren't really part of it until late sophomore/ junior year. It's interesting how having a relatively smaller department affects How Things Are Done.

transition metal craziness

2008-10-06T11:57:00.000-07:00

We're studying transition metal reactions that allow carbon-carbon bond formation in my advanced synthetic organic class (Stille reactions, Suzuki couplings, Heck reactions, pairing Grignards with Ni, basically stuff with copper, palladium, boron, and nickel) and it's cool, but I have a feeling that I'm at a bit of a disadvantage for not having taken inorganic yet. I mean, I know an organic chemist's approach to these mechanisms are very hand-wavy and a "how is this useful for understanding reactions I want to do to make this happen" approach, but I think being used to thinking about metals complexing with ligands and remembering that D orbitals exist would be nice (as a biochem major I'm taking a few core chemistry classes in weird orders because they happen to be at the same time as biology classes...like sophomore inorganic junior year or junior analytical senior year). Ah well, maybe after this spring after I've had inorganic, it will all retroactively make sense. I have a habit of forgetting that there is a periodic table beyond the first couple rows with a few other favorites thrown in, so it's nice to be reminded that there are a lotta elements out there.

science humor

2008-10-06T10:11:00.000-07:00

This joke cracks me up because it's just so bad.

--Why do catholics kneel to pray?
--Because there's no syn elimination in the chair conformation.

yep. pretty bad.

I want to have tea with Mr. Phosphonium Ylide and Mr. Sulfonium Ylide

2008-10-05T21:03:00.000-07:00

Sometimes when I look through lists of organic chemistry terms, especially reactive intermediates,
they seem like they would make for very amusing children's book characters. (I think I may have stolen this idea from a professor of mine, but it intrigues me nonetheless). I mean, there are the common ones...ylide, enol, enone lactone, imine...but what about enyne, ketene, and azirne? You get some goofy looking compounds with some pretty goofy names. I found a facebook group called "Organic Molecule or Pokemon?" that gets to this same idea; organic molecules' names are so goofy that they sound like pokemon.

So I have a test for you, oh readers, without the aid of the internet, between"Phionone" or "Oxepin" which is the pokemon and which is the organic molecule? No cheating.

REU angst/what am I doing with my life angst

2008-10-05T13:42:00.000-07:00

So it's time again to start thinking about REUs/summer research, I suppose. I find this stuff really stressful. I have lab experience, a lot of coursework, but unexceptional grades, and the conventional application route is so goddamn competitive these days--some of my profs say more competitive than grad school. There's some sort of game to play, and I've never been good at figuring out the rules.

Which leads me to think...I kind of don't want to do molecular biology this summer. I have a lot of lab experience with molecular biology through both coursework and summer experiences at UIC (I worked in a biomedical diabetes research lab for a couple summers). I know how to run gels, I know how to use kits, I know how to culture cells. I mean, obviously molecular biology is a big field and there would definitely be something gained from working at a different lab, but I really want is chemistry experience. I have synthetic organic experience, and I really enjoyed it, but that was at Reed (we do solid science at Reed, but it's also science at a small liberal arts school, and there's a whole big world out there); I'd like to see what off-campus chemistry research is like.

Which then leads me to thinking, what type of chem/biochem experience do I want to look for? I have zero experience with structural biology techniques (xtallography or NMR)--just book knowledge, and while I have this vague hunch that I'm headed in a bioorganic/natural products synth/medicinal chemistry/something synthetic organic chemistry with biological applications direction eventually (this is up for change, though, because, as you can tell, my interests are broad, but I guess it's just that I like synthetic organic a lot) perhaps I should see what structural biology is like and think about looking for labs that do xtallography to apply to? On the other hand, I also don't know what synthetic chemistry in a university research lab, or in an interdisciplinary project, or, for that matter, in industry is like at all. Or what about "chemical biology" at the whole biology/chemistry interface? So many faculty webpages. So much cool research. How will I ever wade through all of it?

I also have one foot in chemistry department and one foot in the biology department at Reed. I suppose this is a good place to be, because I can read journals in a variety of disciplines and make sense of them and I have enough coursework to do a lot of different things after I graduate. I keep hoping that having a really interdisciplinary undergrad experience will someday make me a stronger scientist, but we'll see. Sometimes I feel like it's just making me a jack of all trades and a master of none, although I'm still an undergrad, so there's absolutely no reason to be a "master" of anything yet.

But at the end of the day with this sort of stuff, where I end up working this summer is just how the cards play out. And for god's sake, it's only October.

thoughts on problem solving

2008-10-04T01:48:00.000-07:00

Something I've noticed lately: I've gotten really good at certain types of problem solving that I used to suck at. For example, for my structural biochem class, we were given a couple problems on spectroscopy; one was a MS sequencing problem, and the other was a problem with 2D NMRs, asking you to identify chemical shifts of protons in a short peptide via a COSY spectrum and assign the order via a NOESY spectrum.

Now I helped some classmates with these problems, but that sort of problem is exactly the type of problem I would have gotten incredibly tripped up on a year or two ago. Now before biochem, I had never been shown how to interpret a 2D spectrum or a protein MS. But somehow these two problems were relatively easy for me.

I wonder if the skills gained this summer by looking at 1D spectrums of proton NMRs helped (I was doing synthetic organic research, so I basically was running things and then trying to decipher the NMRs). I mean, the strategy you use in interpreting 2D NMRs is quite different from 1D NMRs. Being familiar with chemical shifts of various protons helped, but I think more importantly, despite the details of the strategy being different, it just helped by giving me a set of learned problem solving/critical thinking skills that extend to reading any sort of spectra.

Well, it's good to know that I'm getting something out of this education thing.

88% is a lot

2008-10-04T00:56:00.000-07:00

Thanks to the fantastic blog In the Pipeline I found this article in PNAS about proteins with 88% sequence similarity having vastly different folds. (Apparently, it had been incredible to conceive of a protein with 50% sequence similarity having such a vastly different fold not too many years ago, this review article also in PNAS provided some handy context). Anyway, I'm thinking about writing a term paper for my topics in biochemistry class about this. At first I was thinking it would be about the limitations of just looking at sequence similarity for homology (as I did many many times with BLAST aligns in genetics class), but there seems to be much more powerful concepts to get at here. Because even something vastly different in function can be evolutionarily related. Basically these studies of testing the number of residues that can be changed (either to create drastic changes in folding or to see what the limit in number of residue mutations to retain native folding is) and studying where the mutations must occur is a studying the evolution of different folds of proteins. There could be one fold that is evolutionarily related to another fold via some residue that is mutated whose net result is to switch a helix to a sheet or what have you via how it can make favorable contacts. You could even potentially map out "phylogenies" of sorts of different protein folds to see how they are related to one another. Well, kinda.

Now let's see if I can pull this together to make an awesome term paper instead of a bunch of scattered ideas.

Oh stereochemistry...

2008-10-04T00:02:00.000-07:00

I am and am not a visual person. I like doodles, I like seeing pictures, and I like quick sketches of molecules in a mechanism. But I'm not a terribly spacial person, so converting from 2D to 3D in my head has never been the easiest thing in the world for me. I mean, I'm okay...there are most certainly people who are worse than me...and after practice, parts of chirality, ring-flipping, and eclipsed vs. staggered has become rather intuitive. But more often than not, when it gets complicated I'll pull out the old modelling kit or build it on Spartan.

I've been tutoring sophomore organic lately, and I'm great with explaining how to rationalize acidity and basicity, how to draw resonance structures, arrow pushing, and hybridization effects on geometry. I can make up those problems on the fly, no problem. But the one area I find really difficult to tutor is this really spacial stuff. Because to this day, I occasionally get tripped up when converting a wedge-and-dash diagram to a chair diagram, especially in fused-ring systems. And I don't really have a good systematic approach to it all; it's all a bunch of built up intuition, and when intuition fails, collapsing back on my model kit.

Now I think this has little to do with my abilities as a chemist. We buy model kits for a reason, and even my stunningly knowledgeable organic chemistry professor, Pat McDougal, on occasion uses a modelling kit--he says if it's really important (like for example, it was a compound he was making in his research lab) he doesn't trust his brain. I mean, I recognize the importance of stereochem and conformers but I wonder...is it really necessary to emphasize stereochemistry to the degree they do in first semester organic chemistry?

From what I can tell, assigning Cahn-Ingold R/S notation to carbons and converting Fischer projections in your head quickly is highly dependent just on whether you happen to be a spacial person. I was helping a kid out with this three-ring fused system that had wedge and dash drawings, and it asked you to convert those wedge and dash drawings into chair drawings, labeling axial and equatorial substituients, and hell I got tripped up on it. He told me it took three modelling kits to make that model.

On the one hand, I see how it's important to be tested on that material; it's like IUPAC naming compounds. I can't remember all the rules now and when I'm writing up data I tend to use ChemDraw's "convert structure to name" function, but I can read a reagent bottle and pretty much know what what I'm picking up looks like. I don't think I would have that same facility if at one point I didn't have to memorize all the rules. I don't think anyone would argue that one's ability to name organic compounds has anything to do with one's conceptual understanding of the material--on the other hand, it's an important skill to learn once. Likewise, being forced to really learn how to deal with looking at 2D structures of 3D molecules is important because it is an aspect of chemistry. And it is possible to teach yourself to get better; I've certainly gotten better with practice, so I don't mean to say that it's hopeless if it's not the sort of thing that you get easily.

I guess the problem I have with it is that a lot of people get freaked out that organic chemistry is too hard and isn't something they can do just because they aren't able to do that spacial stuff easily. And a lot of kids that don't have the work ethic to get to the meat and bones of organic chemistry, but just happen to be highly spacial people just "get" it right away and have one "gimme" test. I tell my tutees who struggle with it that stereochem and conformers are important to conceptually understand (I mean it comes up understanding inversion of stereocenters, how a reaction might be thermodynamically controlled, etc.) but if they are having a killer time with this stuff, and it's the sort of problem that they would get tripped up on in the time crunch setting of an exam, it's not what o-chem is all about (additionally I give them advice about what sort of molecules they should make before the exam to bring with them...oh how I've been saved by a pre-made chiral carbon). Success in organic chemistry in the long run is about building up reactivity profiles--and that's what draws people to the subject rather than "is this the R or S enatiomer".

The other thing I find hard to tutor is MO theory, but that's another story all together. One of my professors referred to hybrid orbitals as "chemistry's stork story" for "how does bonding occur?" I know enough hand wavy, descriptive mnemonics to get by, and I've accepted that. I mean, I just did a homework problem about metal-halogen exchanges at cyclopropane rings because "the more s-character, the more electronegative, so the carbanion is stabilized" and that's fine. Ahem...moving on to making things...