Intellectual Merit: Nearly one-third of all sequenced genomes encode integral membrane proteins, which are involved in critical and diverse cellular functions such as catalysis, active and passive transport, and signal transduction. In spite of their importance in biology, the structural characterization of membrane proteins lags considerably behind that of soluble proteins. As part of this CAREER project, a detailed study of the structure and function of a particular enzyme (signal peptide peptidase) that accomplishes peptide hydrolysis chemistry within the confines of the lipid membrane, will be undertaken. Students will determine its three dimensional structure and develop straightforward assays to measure enzymatic activity. In addition, as part of the pursuit of a high-resolution molecular structure, new techniques to facilitate the crystallization of membrane proteins will be developed. Crystal growth is a major rate-limiting step in membrane protein structure determination. The methods developed as part of this proposal will be applicable to the study of other membrane proteins.
Broader Impact: A central aspect of the broader impact of the program is educating, training, and diversifying the future generation of scientists. In addition to mentoring activities and research training for Georgia Tech undergraduate and graduate students, this CAREER project includes a partnership with Westlake High School in Fulton County, Georgia. The PI, a high school biology teacher, and selected Georgia Tech undergraduate Biochemistry majors will collaborate to develop two discovery-based modules for an advanced high school biology course. These modules combine protein science, art and computers, and will be freely available on the internet for all educators. The teacher and high school students will also conduct summer research in the PI's laboratory, and then showcase their results as poster and oral presentations in their school and at science fairs.
