Fishing for chemical answers to biological questions

James K. Chen talks to Molecular BioSystems Deputy Editor Michael Smith about chemical biology, his love for the outdoors and fly fishing

James K. Chen is an associate professor in the Department of Chemical and Systems Biology, Stanford University School of Medicine, US. He uses chemical tools to study developmental biology, including caged oligonucleotides that can regulate embryonic gene expression in zebrafish and other model organisms.

When did you decide to go into chemical biology?

It was when I was an undergraduate, during a lecture given by Stuart Schreiber at Harvard University. He was talking about his work on the immunosuppressive compound FK-506. His laboratory had found that FK-506, and another molecule called cyclosporin, inhibited the activity of calcineurin, a serine/threonine protein phosphatase. These studies were important because they implicated a role for calcineurin in T cell function and provided new insights into how T cell receptor signalling is transduced from the cell surface to the nucleus. After that lecture, I immediately knew that this was the kind of research I wanted to do. I loved organic chemistry, but I was more interested in answering the questions of biology. Using a small molecule to gain insight into a complex biological process was exactly what I wanted to do.

What can chemistry bring to developmental biology?

Chemistry can bring an understanding of biological mechanisms at the molecular level. It enables us to learn what is biologically interesting with molecular clarity. At the technology level, chemistry can help us to break through the natural system, for instance, chemists can make a molecule that doesn’t exist in nature and see the effect it has on a biological system. Chemical technology can break the bounds of biology.

What advice would you give to a chemist who is considering moving into biology?

A key difference between the two disciplines is the degree and level of focus – chemists tend to focus on techniques and they want to understand a system in terms of the simplest model possible; it’s a reductionist approach. With biology, you almost need peripheral vision – the system you’re trying to understand is like a forest, with complexity at many different levels and you have to be aware of it all. Often the simplest answer is not the correct one. Also, there’s a lot to learn, but it’s like learning a new language – if you immerse yourself in it, in time, you can know as much about your particular field as your biology colleagues do.

If you weren’t in this field, where would you have ended up?

I think I would have still been a developmental biologist, but any area of developmental biology is interesting to me. My interest isn’t focused on one particular organism; rather, it’s all about answering the key question: how does pattern form from nothing? It’s about basic architecture. Of course, developmental biology is also related to cancer biology, since many embryonic signalling pathways are dysregulated in tumours, but primarily my interest is fundamental rather than applied.

When you’re not doing science, what do you enjoy doing?

One thing I like to do is run; I normally do a half marathon every three months or so. Also I love fly fishing – it’s my passion. Once a year, I meet up with some old friends from our grad school days and we go fly fishing together. It’s a great way to catch up and enjoy nature at the same time. I love the outdoors so I enjoy anything that gets me out of the office into the natural world.

To read the full interview see Chemistry World and for some of James Chen’s recent research see:

Gene regulation technologies in zebrafish
Hanife Esengil and James K. Chen
Mol. BioSyst., 2008, 4, 300
DOI: 10.1039/b718447f

Chemical technologies for probing embryonic development
Ilya A. Shestopalov and James K. Chen
Chem. Soc. Rev., 2008, 37, 1294
DOI: 10.1039/b703023c

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