|   Electron Microscopy Solutions

Electron Microscopy Solutions

2016 Young Investigator Life Sciences Award Winner

Congratulations to Yuan Gao of the University of California, San Francisco

Thank you to everyone who submitted to our inaugural Young Investigator Life Sciences Award competition. We were very impressed by the breadth and diversity of innovative paper topics. We would like to congratulate our 2016 winner, Yuan Gao of UCSF, for the paper, TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Mr. Gao will receive his cash prize and will be featured in a sponsored talk on his subject at the Washington University St. Louis CryoEM Symposium on May2.

Academic Biography

Yuan Gao is a fifth-year graduate student in the Biophysics PhD program at the University of California, San Francisco. He is a joint student between the research groups of Dr. David Julius and Dr. Yifan Cheng, focusing on structural studies and lipid modulation of TRP ion channels. Mr. Gao and his colleagues recently demonstrated the potential of combining single particle cryo-EM with lipid nanodisc technology to obtain atomic-resolution structures of integral membrane proteins in a close-to-native environment. The study was published in Nature last year and has generated great enthusiasm among researchers in the EM field. Mr. Gao was invited to present his findings at several conferences, including the Biophysical Society Meeting (2016) and the 3DEM Gordon Research Conference (2016).

Before joining UCSF, Yuan Gao obtained a bachelor’s degree in Biotechnology and a master’s degree in Biochemistry from Shanghai Jiao Tong University in Shanghai, China.

Lecture Abstract

When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which lipids play both structural and regulatory roles. Here, we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of an integral membrane protein, the TRPV1 ion channel, in a native bilayer environment. Using this approach, we could ascertain the locations of annular and regulatory lipids, enabling us to show that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting release of bioactive lipids from a critical allosteric regulatory site.