Profile

To put it simply, my group and I study the shape and function of the molecules of life (proteins, DNA and others) — and we sometimes get to try and make them work better or differently. This is only one step in a very complex research-based process the end result of which (an improved/altered plant) is many years away!

If molecules were like everyday objects then my work could be compared to that of a repairman or an engineer – but with a special twist because when you set out to repair a toaster you do not expect any surprises – after all, the toaster was designed by a human being, made in a factory, and there are well-documented schematics available to see what goes on inside. In contrast, macromolecules are made by cells, they are microscopically small so you can’t easily see them or take them apart, and they are shaped (folded) according to rules that we only partially understand. So in my imperfect analogy, I would be an engineer trying to repair (or improve) a radioactive toaster made by aliens: we know more or less what the toaster does, but we do not know what’s inside, or how it functions – and we cannot touch it directly so we have to rely on proxies of some sort (remotes and robots) to handle the device.  Well there’s only so far an analogy would stretch anyway…

This figure is a cartoon representation of a protein I worked on during postdoc  – this protein is called YopM and it is one of several toxins that Yersinia pestis (the Bubonic Plague microbe) produces when it infects its human host. Beautiful and deadly.

Outside of the sciences I pass a lot of my time with family and friends – doing more or less normal stuff such as launching lots of fireworks when the occasion arises (they’re still legal here on Independence Day), shooting videos of microscopic freshwater life-forms, cooking very inadequate food, or making sure that the dog, four cats, and anywhere between eleven and eighteen fish do not eat one another at least in my presence.

In my spare time, of which there is not much, I sometimes answer questions on MadSci.org (which has a very similar purpose to this site).
(read on if not bored yet!)
Every living cell (that we know of) uses (and is built of) a variety of  ‘reasonably common’ molecular components to perform its functions. Why did I put ‘reasonably common’ in quotes? It’s because while overall there are definite themes to these components – such as there are enzymes to convert food molecules into energy, DNA to store genetic code, ribosomes to build new proteins, lipids and proteins to create cell membranes, and so on – when we examine these components up close there is a staggering variety of adaptation and functional diversity within each members of the class. And that’s where structural biology comes in – we study the form and function of these molecules (to the extent that we can since some of them do not hold a particular shape for very long and others are extremely hard to isolate by themselves) and we try to draw parallels between common ones without losing the important distinctive details in the process.

There are several very neat technologies available to us that allow us to ‘look’ inside molecules and study how they work: X-ray diffraction, NMR (nuclear magnetic resonance), and electron microscopy to name the main three.  In my work I rely mostly on X-ray diffraction and a little bit on NMR, for the time being (ask me a question if you want to know more about them).

Once I come to work in the morning I usually get to talk to a couple of my friends/colleagues before setting one foot in the office. Once I get the laptop turned on (it often travels home with me) it is likely to remind me that the first meeting of the day is only a few minutes away, or perhaps a few minutes past.   To paraphrase Bilbo Baggins “I don’t like half of my meetings half as much as I should like, and I go to less than half of them half as much as I should”.

My group members are extremely talented, accomplished scientists with a multitude of highly diversified skills. We work together on common problems but each of us also has a portfolio of work that we do in collaboration with other groups and research teams. Our group meetings are typically dedicated to discussions of  tough problems, planning future work, and figuring out how to accommodate the inevitable excess of things to do into the very finite daily hours.

I work at the bench (although less than I used to) at least some of the time –  I clone genes, purify proteins, set up crystallization experiments, harvest protein crystals and freeze them, or (if things work out well) shoot crystals with X-rays in our home lab or at the synchrotron (if you’re curious why we freeze crystals and shoot them with X-rays – ask me a question!). Above is an example of some of the nicer-looking protein crystals. The rest of the work is computer-based: I have a graphics workstation in my office where I spend a fair bit of my time either making structures or working with them. An example of what a protein structure in the process of being built is shown below . The blue mesh is a contour from experimental data – it shows where electrons of the various atoms in the molecule might be found. The yellow and red lines are chemical bonds (in this case a few Tryptophan, Tyrosine, and other amino acid residues) modeled into the electron density. After a lot of work, a culmination of all our efforts is a structure such as the one shown in the ‘about my work’ section. A collection of all published structures may be found at the Protein Data Bank which is a very good place to start learning about protein structure 🙂

Unlike many of my friends and colleagues, I do not drink coffee at work – instead I get most of my caffeine from diet soda.