James S. Fraser, Ph.D.

Research

The goal of my lab is to understand how enzymes function in action.  Enzymes are flexible protein machines that change shape as they work: these contortions allow enzymes to grab and manipulate molecules on which they act, and release a chemically altered product. But traditional techniques, such as X-ray crystallography, often do not capture these structural gymnastics, instead yielding a static image of an enzyme in one time and place. That failure is due, in part, to the fact that to image the enzymes, they are literally frozen to limit damage by the X-rays used to see them. As a graduate student, I showed that conducting X-ray structural analyses at room temperature revealed a range of “hidden” movements in enzymes. Now, my laboratory will attempt to capture how enzymes shift shapes as they engage in their chemical duties, and assess how mutations that disturb their activity alter their movement. This work stands to advance the field of structural biology and could lead to the production of molecules designed to restore the motion and function of proteins involved in human diseases or to combat pathogens that are resistant to current antibiotics.