We are interested in how the lipids of a membrane regulate the function of membrane proteins such as SNAREs, Rab GTPases and ABC transporters.
Our laboratory is interested in how the lipid composition and physical properties of a membrane affects protein function. To this aim we look at membrane fusion using vacuolar lysosomes from baker’s yeast. Although the final catalysts of fusion are SNARE proteins, very little work has been done to examine how the physical state of the membrane affects these proteins. Some work has been done describing the attachment of lipid binding domains to the bilayer, which is a direct chemical effect of the membrane on proteins. However, the membrane can also regulate proteins through physical effects that include membrane compression, line tension, curvature and hydrophobic mismatching. It is clear that SNARE interactions are very different in solution compared to biologically relevant membranes and that the physical regulation of SNAREs largely occurs through transmembrane domains.
Fusion events are often carried out in highly organized membrane platforms, collectively known as membrane microdomains. These microdomains are typically enriched in regulatory lipids that partition from bulk lipids (e.g. phosphatidylcholine) that make up a vesicle. Although low in abundance, regulatory lipids are critical in cellular signaling and the organization of membrane microdomains. The regulatory lipids that drive microdomain assembly include diacylglycerol, phosphatidic acid, ergosterol, phosphoinositides and sphingolipids. Microdomains have unique chemical and physical properties and are hotspots of lipid metabolism and signal transduction. The stoichiometry of microdomain lipids is constantly changing through the action of lipid phosphatases, kinases and lipases. Lipid metabolism and remodeling cause drastic changes to the local physical properties of microdomains. These changes can alter membrane curvature, fluidity, bilayer asymmetry, thickness, bilayer stability and elastic compression. Thus, protein function can be allosterically regulated by changes in the membrane.
B.S., 1992, California State University, Long Beach (Medical Microbiology)
M.S., 1996, California State University, Long Beach (Microbiology)
Ph.D., 2002, University of Michigan, Ann Arbor (Microbiology and Immunology)
Postdoc., 2002-06, Department of Biochemistry, Dartmouth Medical School
NIH Pre-Doctoral Fellow, 1999-2001
Helen Hay Whitney Postdoctoral Fellowship, 2003-2005
University of Illinois Research Board Arnold O Beckman Award, 2011-2012