Culture gap: synthetic chemists and learning biology

I started responding to this comment:

Now that you have invested so long to transform in to a 'chemicalbiologist', would you mind suggesting some quick tips from your journey for the people ho want to take the same path? Are there any books or some crash courses etc?

And got so in depth that I decided to make it a post of its own. So here are my thoughts about where to start to develop better flexibility as a synthetic chemist who wants to work on bilogical problems.

The best crash course I got was weekly lab meetings in a lively, rigorous yeast genetics/molecular biology/kinase signaling lab (one of my postdoc labs). I started out so clueless that I felt like I was on Mars for the first year and a half or so. But because the people in that lab were so open and helpful, and the PI is an engaged, active teacher, they helped me learn the "language" of biology-type ways of thinking and data/information representation.

It's that language that you really need as a chemist moving into biology. And by "language," I mean more than just terminology (although that is a big part of it). It's also a change in visualization of information and getting better at logic puzzles. Imagine a multi-step synthesis with a blank at step 2, where 4-5 possibilities (which you have assumed based on either mechanism or other times people have done similar things) could fit in there to result in the product (or mixture thereof). In biology, you have to come up with ways to test *which* of those possibilities comes from the retrosynthetic direction (for which you are only postulating a route) and will result in the product(s).

In all of this you also have to accept that: a) your only measurement techniques are indirect, i.e. you usually can't just analyze the structures with some direct spectroscopic technique and figure out what they are; and b) your assumptions might be wrong. So you have to do lots of control experiments where you also assume some certain set of reagents should DEFINITELY give the products, and some other set should DEFINITELY NOT. That gives you yet another indirect way to make you feel more comfortable with your assumptions. The hardest part for many chemists is having to be okay with indirect information. The second hardest part is having to remember that if your "result" gives you something analogous to "75% yield of the product," you still have to think a lot about WHAT molecules/interactions are represented in that other 25%. You can't just purify it away and pretend it didn't exist.

Getting used to reading gel electrophoresis/Western blot (antibody detection) data, as well as biological "cartoon" format (where you mostly worry about conceptual connections, and not so much molecular mechanism and byproducts etc.), are some great ways to start. But you'll probably need a coach to guide you through it and translate how the experiments work and what the results mean. Finding friendly, sharp biologists (whether faculty, postdoc or grad student--it doesn't pay to be snobby about this, sometimes the trainees are gonna be WAY better at teaching you! Just make sure to credit them or repay them somehow!) can be the difference between this working vs. not working.

NIH mentoring and grantwriting workshop (UPDATED 10-23-09)

I am spending the next three days at a secret location for an NIH conference grant/Program Officer-run grantwriting and mentoring workshop. Anything that is not confidential (i.e. pertaining to the specific research information shared there by proposal donators and other attendees) and might be useful to people here, I will share either as I go or after we're done! I'll just keep updating this post with info.

UPDATE 10-24-09: To address a good point that CPP made but also highlight what the workshop was really about, I updated the wording about "a compelling human health relevance."

UPDATE 10-23-09: This workshop was particularly focused towards junior faculty in synthetic organic chemistry, bioorganic/bioinorganic chemistry and chemical biology. I'll give snippets of stuff about different things we learned/talked about and experiences we had as I have time. Right now I have 5 minutes, so I'll tell you about the major NIH R01 take-home message from the workshop. The key, especially for chemists and anyone who does basic synthetic research that is not necessarily easy to connect to a disease, is to establish a credible, compelling human health relevance through developing a depth of understanding and solid rationale within the biology you want to study.

If you love inventing new ways to make complex natural products, it is NOT ENOUGH to just say "this natural product is interesting because it kills a cancer cell line with a potent IC50 and came from a sponge." Nor is it quite enough to say "This methodology is interesting because it would allow access to chemical structures or information about biological function that is hard to get otherwise." You really have to craft a strong argument for WHY your particular methodology or hypothesis is fundamentally important to the study or treatment of a human health problem at whatever level your work can fit, for example:

  • tool-development for basic biological research
  • novel methodology for accessing difficult molecular architectures that can probe or affect biological function

as well as HOW it represents a new angle for approaching the problem. Once you lay that groundwork in the beginning through the specific aims page, "significance" and "innovation" sections, THEN you can get more into the details of your specialty. But no amount of beautiful chemistry or insightful methodology will get you past the hurdle of not finding a compelling connection to a disease-related biological knowledge gap.