Medical Student Research Fellowship for Summer 2010

Mentor: Mike Brown and Joe Goldstein
Department: Molecular Genetics
Room number: L5.238
Mail Code: 9046
Phone number: 214 648 2141
E-mail: Mike.Brown@UTSouthwestern.edu and Joe.Goldstein@UTSouthwestern.edu

Project title: Biochemical Analysis of Cholesterol Transfer
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic Research

Brief Description of Project:
Export of lipoprotein-derived cholesterol from lysosomes require 2 cholesterol-binding lysosomal proteins: membrane-bound NPC1 and soluble NPC2. The binding site of NPC1 is located in its N-terminal domain (NTD) that projects into the lysosomal lumen. After hydrolysis of cholesterol esters by lysosomal acid lipase, NPC2 binds the free cholesterol, then transfers it to the NPC1(NTD). How the cholesterol then moves to exit the lysosome remains unknown. By using purified NPC1 or membranes enriched with NPC1, we will be studying the role of the remainder of the NPC1 protein in the movement of cholesterol from NPC1(NTD). The project will involve overexpression of proteins in mammalian and insect cells, purification of recombinant proteins, and in vitro assays of cholesterol binding and transfer.
Previous Research Activities or Publications with Medical Students: