ChBE Seminar Series: Thomas R. Fuerst
Tuesday, November 24, 2015
11:00 a.m.-12:15 p.m.
Room 2108, Chemical and Nuclear Engineering Building
Professor Dongxia Liu
Thomas R. Fuerst, Ph.D.
Professor and Director
Institute for Bioscience and Biotechnology Research
University of Maryland
Toward development of structure-based vaccines and next-generation therapeutics
The Institute for Bioscience and Biotechnology Research (IBBR) is focused on bringing together expertise at the forefront of biomolecular science and engineering to advance promising research and to facilitate translation of innovations to real-world applications. This talk will focus on our recent progress in development of structure-based vaccines and next generation protein therapeutics. Most, if not all, of the licensed human vaccines have relied heavily upon the antigen existing in the native or natural form in order to stimulate protective immunity against the pathogen. However, many of the “vaccine-difficult” pathogens have co-evolved strategies to stimulate immune responses to “immunodominant” sites that are immediately adjacent to, but not centered on, critical antigenic determinants that elicit neutralizing antibodies to the pathogen (e.g., HIV, hepatitis C virus, etc.). In the first part of my talk, I will discuss our results in the structural characterization of the HCV E2 envelope protein and identification of epitopes capable of eliciting protective antibodies against this highly diverse virus. In particular, I will focus on the structural characteristics of a region of the E2 protein (Domain E) to which a broadly neutralizing human monoclonal antibody can penetrate a glycan shield of HCV, while the virus can evade other neutralizing antibodies to this same region. In the second part of my talk, I will discuss the design concept of a novel class of therapeutics called SMART molecules. Computation-based protein design has been used to create binding scaffolds that are also functional by nature using the cellular target RAS as a model system. Our engineered SMART molecule exploits the conformational difference in oncogenic, mutant RAS that gets stuck in an activated state causing hyperactivity of the downstream signaling pathway that drives tumorigenesis. Multiple levels of regulation can be achieved using this system that can sense binding to mutant RAS and trigger the release of an activated protease against this target.