About me

I’m fascinated by the macromolecules of life: proteins, RNA, and DNA. Although composed of simple building blocks, evolution has furnished them with complex structures and functions. From a biophysics perspective, biomacromolecules are akin to machines, with moving parts and discrete functional components. Thus to understand them we need to determine their three-dimensional structures. However, structure is not enough. Although more than 100,000 structures have been determined by high resolution techniques like X-ray crystallography (MX) and cryo-electron microscopy (cryo-EM), the design principles invented by evolution are so varied and complex that they are seldom apparent from the structure alone. For this reason, structural biology has sought methods to make molecular movies. Traditional MX and cryo-EM reveal single snapshots, representing one possible conformation. Broadly speaking, my research uses advanced X-ray scattering and cryo-EM techniques that are sensitive to the correlated motions of proteins in solution and in crystals. By deconvolving the mixture of signals in such datasets and building physical models, we have revealed how protein structures fluctuate away from their average conformations. Going forward, my goal is to apply these methods to better understand enzyme function and regulation. By revealing how dynamics confer function, we can begin to rationalize nature’s design principles, vastly increasing the explanatory power of structure determination.