Event
Bioengineering Seminar Series: Matt DeLisa
Wednesday, December 10, 2008
2:00 p.m.-3:00 p.m.
Room 5112 Plant Sciences Building
Professor William Bentley
(301) 405-4321
bentley@umd.edu
Please note the special day, time and location.
Exploiting Quality Control Mechanisms that Regulate Protein Folding and Transport
Presented by Matt DeLisa
Assistant Professor, Chemical Engineering
Cornell University
All organisms, including bacteria, localize a fraction of all of their proteins partially or completely outside of the cytoplasm. Along the way, these proteins must cross at least one hydrophobic lipid membrane. The remarkable feat of delivering proteins across tightly sealed membranes is achieved largely by complex secretion machineries known as translocons. The bulk of protein transport across the inner cytoplasmic membrane of bacteria is facilitated by the well-known general secretory (Sec) pathway, but additional modes for transport into or across the inner membrane exist, including the recently discovered twin-arginine translocation (Tat) pathway. During both Sec and Tat transport, a variety of quality control checkpoints ensure that only proteins that pass a stringent selection process are allowed to enter the transport cycle thereby preventing any harmful effects that might be caused by the deployment of export-incompetent proteins (for a review, see Fisher & DeLisa, 2004 J Bacteriol). Our studies in this area focus on fundamental and applied aspects of quality control mechanisms that regulate the transport of proteins into and across biological membranes. We are currently exploiting the protein folding quality control pathways of bacteria to (1) engineer "superproteins"high-performance proteins that ignore at least some biologically imposed restrictions on amino acid sequence and occupy regions of sequence space unexplored by proteins optimized for in vivo function; and (2) create potent new protein therapeutics and vaccines. In parallel, we are exploiting our ever-increasing awareness of the factors influencing protein folding in bacteria to engineer "better-folding cells" by re-designing the intracellular landscape in a manner that universally improves the efficiency of the folding process.
