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Our efforts are focused on structural biology applications of an advanced proteomics technology developed at UC San Diego, enhanced hydrogen/deuterium exchange mass spectrometry (DXMS). Our goal is to provide DXMS as a readily accessible tool for collaborating investigators interested in applying it to important issues in protein structure and dynamics. It can be used to rapidly determine the high-resolution structural dynamics of proteins, alone or in combination with other proteins, DNA, or small-molecule ligands. A typical study can be completed in 2-4 months employing a few hundred micrograms of the study protein. Collaborators provide the study protein and experimental questions, and design the experiments with us. We then perform most aspects of the DXMS data acquisition, and interpret the results in concert with the collaborator.

We now work with eighteen collaborating graduate students and post-docs, who first rotate through our DXMS resource where they learn the theory and practice of DXMS while acquiring and processing data on their study proteins. When they return to their parent labs, the trainees are fully able to continue the same or additional DXMS studies with us remotely. Some collaborators have subsequently set up their own DXMS instrumentation with our guidance.

In just the past year, these students' work has resulted in 10 top- tier DXMS- focused publications (with 5 more manuscripts under review) and has supported the acquisition of more than $6M in new NIH funding to support ongoing DXMS studies of their proteins of interest. Perusal of these publications makes clear the wide range of structural/ protein dynamics issues that can be directly addressed with DXMS study. Students who rotate through our lab leave with cutting-edge expertise in DXMS analysis that is readily applicable to any protein of interest to them.

Track(s):
Molecular Pharmacology
MCB