Seminar Titles & Abstracts
Scientific Research Seminars
Structure, Folding and Functional Studies of Opacity-Associated (Opa) Proteins from Neisseria gonorrhoeae
The family of Opa proteins from Neisseria gonorrhoeae and N. meningitidis are eight-stranded beta-barrel proteins that induce phagocytosis of the bacterium by engaging three different host receptors: carcinoembryonic antigen cellular adhesion molecules (CEACAM), heparansulfate proteoglycans (HSPG), or integrins via HSPG and fibronectin or vitronectin. The receptor engaged depends on the sequence of two of the extracellular loops (termed hypervariable (HV) loop 1 and 2), which are highly variable between isolates. There are multitudes of HV sequences identified; however, only approximately 25 Opa protein sequences have been characterized in terms of receptor engagement. Multiple sequence alignment of the HV loops does not reveal specificity motifs among the family of Opa proteins due to the extreme variability in the amino acid sequences. The solution NMR structure of Opa60 from N. gonorrhoeae that interacts with CEACAM1 receptors to induce phagocytosis reveals that the beta-barrel is a canonical eight-stranded beta-barrel and the HV loops are long, disordered, and highly dynamic. The NMR solution structure, coupled with in vivo Opa reconstituted liposome assays, has facilitated investigations of the molecular determinants of Opa-receptor interactions.
Membrane protein structural biology: from micelles to bacterial invasion
The research aims of the Columbus laboratory are two-fold: (1) to address the challenges in membrane protein structural biology and (2) to investigate the structural determinants of bacterial pathogen – host interactions mediated by membrane proteins. Specifically, the structures of N. gonorrhoeae and N. meningitides Opa proteins, which interact with host proteins and induce pathogen phagocytosis, are of interest. However, in order to investigate the structures of these proteins, as well as the complexes with the host receptors, methods for accelerating structure determination are being developed. A major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics the native lipid bilayer. Currently, detergents are selected by exhaustive screening because the effects of protein-detergent interactions on protein structure are so poorly understood. The overall goal is to use a multifaceted approach (NMR and EPR spectroscopy, small angle X-ray scattering, and X-ray crystallography) to develop a fundamental understanding of the protein – detergent interaction in order to accelerate the structure determination of membrane proteins involved in bacterial pathogenesis. Results arising from our current pursuits of this overarching, long-term goal will be presented.
Teaching and Research: a symbiotic relationship
Often the three pillars of academia (research, teaching, and service) are considered to be independent endeavors by faculty and administrators. This notion of mutual exclusivity likely stems from the finite time that an individual academic has to devote to each area. However, there is synergy between research, teaching, and service that can maximize time, improve student learning and training, and produce quality federally-funded research programs. In this presentation, I will present motivations and philosophies and developed programs that demonstrate the synergistic relationship of teaching and research. In addition to why I think this synergy is important to both student and faculty, I will specifically discuss an undergraduate biochemistry research-based laboratory curriculum, a research laboratory design that emphasizes learning and teaching for both graduate and undergraduate students, and how to incorporate experimental design and research into science curricula.