University of California, Irvine
Associate Editor
Biophysical Reports
What are you currently working on that excites you?
I have a collaboration with a pharmaceutical company to study the mechanism of action for a new class of drugs to treat sickle cell disease by binding hemoglobin and preventing fiber formation. This drug has been described as life-changing for individuals with this painful and damaging condition. Crystallography has shown that the protein structure does not change substantially upon drug binding, leaving many questions about how the drug influences the protein in solution. Our industry-sponsored project will use NMR spectroscopy and other biophysical techniques to understand the effect of drug binding on protein stability and dynamics.
What has been your biggest “aha” moment in science?
My lab determined the structure of the Neurite Outgrowth Inhibitor (NOGO) protein. The extracellular part of this protein is active so we chose to work on that fragment. I asked my student, Jessica Schulz, to perform a measurement of residual dipolar couplings (RDCs) to enhance the structural information we had on this system. The RDC experiment uses lipid bicelles in a liquid crystal form. A few weeks later, I asked Jessica about the results and she told me that the experiment did not work since all of the protein signals disappeared every time she added the lipid bicelles. Although she interpreted this as a failure, I was very excited since it indicated that the protein could be binding to the lipid bilayer, even in the absence of the two flanking transmembrane helices. We confirmed that NOGO does associate strongly with membranes even though it does not have a canonical lipid-binding motif. In this case, lipid interactions drive the structure of the protein to form.