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Interview: Shining a light on the proteome
20 January 2009
Ben Cravatt talks to Michael Smith about his research into the function of the proteome and success in cloning the cDNA of a hotly pursued enzyme
Benjamin Cravatt is a professor and chair of the Department of Chemical Physiology at The Scripps Research Institute in California, US. His research combines synthetic organic chemistry, proteomics and metabolomics. He is a member of the Molecular BioSystems editorial board.
What inspired you to be a scientist?
There wasn't a plan from birth, but my Dad, a dentist, and my Mom, a dental hygienist, inspired me to think about biology. I went to Stanford University in the US with a view to going to medical school. My major subject was biology and I got the chance to work in John Griffin's bio-organic chemistry lab. That inspired me not only to do research, but also to work at the interface of the chemical and biological disciplines.
How did you decide what to do at graduate school?
Most graduate programmes in the early nineties were very restrictive. You were expected to see yourself as a chemist or a biologist and encouraged to pursue a sub-discipline in one of these subjects. However, the Scripps Institute in California aimed to keep their students as dedifferentiated as possible. Students were allowed to use whatever technologies they wanted to address problems at the interface of medicine and molecular sciences. I started at Scripps and never looked back!
Would you describe yourself as a chemical biologist?
Yes: to be a chemical biologist, you have to appreciate how chemistry and biology are performed to address difficult problems. From a synthetic chemistry viewpoint, this means knowing how to make a molecule that requires more than one step to synthesise. From a biology perspective, it might mean trying to enrich and purify a protein sufficiently to get sequence information to determine its primary structure. Both were aspects of my education at Scripps. Despite not considering myself a card-carrying synthetic chemist or pure biologist, I had sufficient experience in both fields to tackle problems that others couldn't.
What did you do after your PhD?
I'd been fortunate in graduate school to succeed in purifying the enzyme fatty acid amide hydrolase (FAAH) and cloning its cDNA. FAAH degrades endogenous lipids in our nervous system involved in interacting with the cannabinoid receptor. It was a hotly pursued enzyme by several labs and we just happened to use chemical approaches to enrich it using synthetic inhibitor columns. This gave us the opportunity to dive into that field with a unique set of tools. At that time, the Skaggs Institute for Chemical Biology started at Scripps was keen to bring in young people and I got the opportunity to join the faculty.
What kind of research do you do?
What aspects of mammalian biology are you interested in?
We're interested in enzymes that regulate small molecule metabolism and signalling pathways. Such enzymes are a rich source of interesting new biology and potential therapeutics. If you look at the number of enzymes for which there are drugs on the market today, more than 70 per cent perform chemistry on small molecules. There was a great review a few years ago by Robertson that discussed this.1 Metabolic pathways that regulate similar molecules in mammals tend to be in pathways controlling higher-order behavioural/physiological functions and their perturbation can produce effects on processes ranging from inflammation to cognition and depression. Monoamine oxidase and COX inhibitors are excellent examples of drugs that perturb enzymes that regulate small molecule signals. I think that's a great area for chemical biologists to exploit because you have enzymes that are druggable and the pathways they regulate are essentially organic chemistry.
How do you think this field is going to develop?
If you weren't a scientist, what would you be?
I don't think any other job would inspire me as much. There's freshness and a drive when working with talented colleagues in an environment that is always changing. However, I was a competitive athlete at college, which I miss, so if I wasn't a scientist, maybe I'd dream of being a professional athlete.
References1. J. G. Robertson, Biochemistry, 2005, 44, 5561.
The Cravatt Lab
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