CAREER: Discrepancies in raft size between cellular and model membranes: Solid-state NMR measurements of protein effect on lipid raft size

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

In this CAREER award, funded by the Experimental Physical Chemistry Program of the Division of Chemistry, Professor Megan Spence proposes to study the role of membrane proteins in modulating the size of lipid rafts in the cell membrane. Lipid rafts are hypothesized to play an important role in the organization of proteins in the membrane, actively orchestrating protein-protein interactions by sequestering particular membrane proteins while shunning others. To measure the size of the rafts, she will develop a diffusion-based technique combining solid-state NMR spectroscopy with magnetic resonance imaging (MRI), capable of measuring rafts as small as 200 nm. The apparent diffusion of lipids in a raft is constrained by the lipid raft boundaries, and the size of the rafts will be measured by determining the maximum root-mean-square displacement of the lipids. The proposed work will develop solid-state NMR spectroscopy as a biophysical tool for the study of membrane rafts, and further our understanding of the role of lipid rafts in modulating protein function and the role of proteins in modulating lipid raft formation. Detailed information about lipid raft-protein interactions will help medical researchers better understand raft-related diseases like viral infection and prion diseases. Professor Spence will develop a one-credit practical laboratory techniques class for second year undergraduate students, focusing on laboratory culture, good notebook keeping, and planning of experiments. To practice these skills, students will design experiments to be carried out in an Earth's-field MRI. Early exposure to research increases the retention of science majors, particularly those of underrepresented populations, and this course poises sophomores for research work in the following summer.