PLoS journals

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"

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).

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.

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

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.

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

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

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?

"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.

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

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.

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

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?

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?

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.

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

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

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

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

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

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

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

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...

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...