Research Assistant Professor
B.A. Middlebury College, 2004; Ph.D. Oregon State University, 2011; Post-doc: Oregon State University, 2011-2012; Post-doc: Cornell University, 2012-2016
Honors and Awards
NIH Ruth Kirschstein Post-doctoral fellowship, 2013-2015; Oregon State University P.F. and Nellie Buck Yerex Graduate Fellowship, 2010
Structural Biology, Protein Engineering
Understanding protein function at the molecular level informs us how cellular life works and also allows us to create proteins with new or enhanced functions for scientific, medical and biotechnological purposes. My research uses a unique combination of structural biology and protein engineering to accomplish these goals, with particular emphasis on the development and application of a rapidly growing technology called non-canonical amino acid (ncAA) incorporation in which amino acids with unique functionalities are incorporated into proteins. Though powerful, this technology can be limited by low efficiency due to impaired activity of engineered tRNA synthetases and their interactions with tRNA. As part a technology development project, we use a combination of x-ray crystallography, structure prediction and enzyme kinetics to optimize tRNA synthetase activity in order broaden the utility of the technology. We then use this technology to study the function and metabolic fate of proteins damaged by reactive nitrogen species in diseased or oxidatively stressed cells. When tyrosine residues are damaged in this way, 3-nitrotyrosine is formed and the function of the protein can be changed. This post-translational modification is analogous to phosphorylation, yet unlike phosphorylation little is unknown if and how these nitrated proteins are degraded or recycled back to their original state when oxidative stress ceases. We aim to develop sensitive and specific biosensors that monitor protein nitration is cells and reveal the fate of these proteins using site-specifically incorporated nitrotyrosine amino acids in biologically relevant systems.
My second area of interest lies the study of bacterial biofilms. Approximately 80% of chronic bacterial infections are caused by biofilm forming pathogens, in large part because the self-produced biofilm matrix surrounding the bacteria protect the community from their environment, the host immune system and antibiotic insult. The transition from biofilm to planktonic lifestyle is a well-regulated process involving many receptors that sense and respond to the cell’s environment, yet little is known about the mechanisms by which these receptors transmit information across cellular membranes to regulate biofilm formation. Transmembrane proteins, however, are notoriously difficult to study and few methods exist to improve their tractability. To overcome this challenge, we use ncAA technology to create a suite of facilitator proteins that, when covalently complexed with membrane proteins, enhance their likelihood of crystallization, and aid in the topological analysis of low resolution structural envelopes. These techniques allow us to study these and other receptors at a highly detailed level, so that we ultimately can develop new strategies to manipulate their activity and help treat chronic infections.