NSF Award
1244236
Intellectual Merit. Biological membranes surround all living cells, confine their internal organelles, and participate in an astounding variety of essential cellular functions, including extracellular signaling, electrolyte balance and energy conversion. These membranes are structurally and chemically heterogeneous environments composed of numerous types of lipids arranged as a continuous bilayer, in which membrane proteins are either embedded or surface-associated. The goal of this project is to understand the effect of the lipid bilayer on the structure and function of the membrane protein gamma-secretase. This protease is of great importance as it is responsible for activating numerous signaling molecules involved in the regulation of neuronal function, and its substrate specificity is thought to vary with the bilayer composition. Using novel assays the research will study the effect of physical and chemical parameters of the bilayer on secretase activity. To visualize the structure of the enzyme in a membrane it will be crystallized in lipid bilayers and analyzed using electron microscopy. This project constitutes a paradigm shift in membrane protein research as it moves away from commonly used artificial detergent systems to the study of membrane proteins in their natural lipid bilayer environment.<br/><br/>Broader impacts. By training scientists in membrane protein research and in the principles and applications of modern structural biology, this project will provide a platform for educating the next generation of scientists at the interface of biophysics, biochemistry and biology. The PI will continue to teach electron microscopy in a course available to students from all New York City institutions. Additionally, facilitating and encouraging minority participation in the sciences through teaching, mentoring and career counseling is a key goal of this project. This project will recruit students from various backgrounds at different career stages, through existing programs such as Post Baccalaureate Research Education Program (PREP), the Summer Undergraduate Research Program (SURP), and the precollege and collegiate programs of the Center for Excellence in Youth Education (CEYE). Emphasis will be placed on raising the scientific literacy of the public by ongoing outreach activities and by hosting one local high school student every year. This student will be chosen through an ongoing collaboration with the science faculty at Great Neck South HS.
