David Stokes
New York University School of Medicine

Associate Editor
Biophysical Reports

What are you currently working on that excites you?

Imaging of macromolecular machines under turnover conditions. This is old hat for single-molecule people, but I’m born and raised a “structural biologist” with a legacy of using inhibitors and mutations to lock the machine in a defined conformational state. The resulting homogeneity in the population of molecules is necessary for crystallization and very helpful for cryogenic electron microscopy (cryo-EM) analysis. But the increasing capabilities of cryo-EM make it possible to segregate individual reaction intermediates from a population of proteins that are actively cycling through the steps of the reaction. Not only does this guarantee native conformations that are relevant to catalysis, but like single-molecule data, it provides information about the kinetics of the reaction, based on the relative numbers of molecules occupying each intermediate state at the moment of freezing.

At a cocktail party of non-scientists, how would you explain what you do?

I have always made a serious effort to explain my science to anyone who will listen. My feeling is that everyone can, and should, understand the underlying principles. The trick is simply not to get technical and to find analogies with the macro world that are generally taken for granted. In that regard, I liken the island of Manhattan to a cell, surrounded by a ring of highways akin to the cell membrane, with the rivers representing the extracellular milieu. Given my research interests, I like to try to convey the idea that proteins act as machines that accomplish everyday tasks: garbage trucks (proteosome), trains and buses (cytoskeletal motors), power stations (mitochondria). Even the physical scale is not so far off. Given the lack of clear compartmentalization, I have to admit that Manhattan is more bacterial than eukaryotic. If I still have their interest, then we move to a particular machine, which requires a different analogy.