|Jeremy Berg at Glacier National Park in the summer of 2010. Photo courtesy of Berg.
Jeremy Berg has kicked off his tenure as the 83rd president of the American Society for Biochemistry and Molecular Biology. Berg’s career has straddled academia and government. He began his independent research career in the department of chemistry at Johns Hopkins University working on zinc-finger proteins. At the age of 32, he was appointed director of the department of biophysics and biophysical chemistry at the Johns Hopkins School of Medicine, making him one of youngest department chairs in the university’s history. In 2003, Elias Zerhouni, then the director of the National Institutes of Health, tapped Berg to head the National Institute of General Medical Sciences, which he did for eight years. Berg has been at the University of Pittsburgh for a year now, a move he famously made as the “trailing spouse” to support his wife’s career. He is the university’s associate senior vice-chancellor of science strategy and planning and holds a faculty position in the department of computational and systems biology. Berg spoke with ASBMB Today about his current research interests; the influence of his wife, radiologist Wendie Berg, on his work; and his view of the current scientific landscape. Below are excerpts from the interview, edited for length and clarity.
Your research at the University of Pittsburgh is focused on peroxisomes. How did you get interested in them?
Berg: It’s a project my lab (at Hopkins) started over a decade ago. It was brought to my lab by an M.D./Ph.D. student who had done a rotation in a cell biology lab that was working on peroxisomes. He was interested in trying to understand the structural basis for targeting signal recognition. The molecules that were involved in the process had been identified, and the question was, “What’s the structural basis for the recognition?” We solved the structure of the complex between the receptor protein and the targeting peptide over 10 years ago and have been working on it pretty much ever since. At Pitt, I’m mostly focused on using computational methods to understand a lot of the data that we’ve accumulated over the years. We’re working on why particular peptides bind more tightly than others and testing state-of-the-art methods for calculating binding affinities from structures.
What have you found so far?
Berg: We have looked at all the proteins in the human proteome that have the most common type of targeting signal. There are approximately 50 different proteins. We found the affinities ranged over almost four orders of magnitude. We discovered there was a very suggestive correlation between the affinity of targeting signal and the abundance of the mRNA. The more abundant proteins have lower-affinity targeting signals, and less abundant proteins have higher-affinity targeting signals. It makes sense from a chemical and biochemical point of view.
How do you see the landscape of biochemistry and molecular biology now?
Berg: It’s now possible, both technically and intellectually, to think not just about one protein and one ligand at a time but to think about a whole system. We can really understand how the pieces compete with each other and fit together. We can connect the individual molecular interactions with biochemistry and physiology.
How would you say science has evolved over the course of your career?
Berg: When I was first starting out, there were completely unknown classes of proteins that are now well characterized and contain large numbers. I started off my independent career working on zinc-finger proteins after the first of those proteins was discovered in frogs. Within the first year or so, it became clear that there were members of the same family in other organisms, such as Drosophila, yeast and humans. Within a few years, it was clear it was one of the largest, if not the largest, families of proteins in many eukaryotic organisms. Those sorts of trends have occurred across many different fields.
Another big change is it used to be that biochemistry was much more of a data-gathering problem. These days, with a lot of new technology, data gathering is much more straightforward. People are generating vastly more data than they have time or ability to analyze. That’s one of the reasons why I ended up going to a department of computational and systems biology. There are so many data out there waiting for new tools to be analyzed.