When can we start calling ourselves an "ist"?

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

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:

Pictures tell this story better than words

pKas

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

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?

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.

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.