Award
NIH Reporter #3R35GM147095-05S1
Molecular mechanism of regulation and activation of membrane proteins in native membrane milieu
Recipient
Yale University, School of Medicine, Department of Pharmacology
Award Amount
$84,742.00
Ceiling
$84,742.00
Awarded
July 22, 2026
Identifier
3R35GM147095-05S1
The award funds research to develop methods for studying membrane proteins in their native lipid environment, focusing on KRas and Trk proteins, to understand their regulation and implications for diseases like cancer and neurodegeneration.
Description
This project aims to develop an experimental pipeline to study the molecular mechanisms regulating membrane and membrane-associated proteins within their endogenous environment. The approach involves extracting membrane proteins while retaining their local protein and lipid interactome using native nanodiscs formed by styrene-maleic acid copolymer (SMA). The study will focus on two clinically relevant proteins: KRas, a small GTPase oncogene, and Trk family receptor tyrosine kinases involved in neuronal survival and pain perception. The research will utilize techniques such as single-molecule TIRF microscopy, native mass spectrometry, lipidomics, proteomics, and structural studies to analyze the biophysical and biochemical properties of these proteins in their native membrane microenvironment.