Insights from Austin

Prof. Glenn Millhauser (University of California, Santa Cruz) used DEER to examine the conformational distributions of another membrane transporter, cystinosin. Mutations of this transporter disrupt the passage of vital materials across the cell membrane, leading to the genetic disease cystinosis. Using EPR distance measurements, the conformations of this transport protein were observed and compared, revealing the impacts of such mutations on the functional conformations of the protein – and therefore providing insight into the mechanism of disease and introducing potential therapeutic avenues. The work encompassed a multitude of measurements, emphasizing that speed and throughput are vital considerations when tackling tough problems in complicated macromolecules. A wealth of data can enable holistic analyses and aid in the deconvolution of multifaceted systems. Continual improvements of the speed and sensitivity of EPR experimentation will help broaden its reach to similarly relevant problems and diseases.

 It was also a scientific and personal pleasure to see the collective works of Prof. Sunil Saxena’s lab (University of Pittsburgh, my alma mater). While I do have a bias, their work was undoubtably noteworthy with four talks involving sensitivity gains in EPR distance measurements, optimizing experimental setup to account for orientational effects, and combining EPR data with advanced molecular dynamics simulations for conformational interpretation. These presentations ran the full gamut of the scientific process, improving upon experimental design, data acquisition, and structural analysis. It’s amazing the progress that can come in a few short years, and there is no doubt that we can go even further in the pursuit of experimental efficiency.