Candidate: Dr. Jaye is a trained pathologist who will pursue an academic career in basic research, and plans to maintain his research focus on selected aspects of neutrophil biology. He will seek a position in which he can practice as a physician scientist with 75% effort in research and 25% in diagnostic molecular hematopathology and flow cytometry. The current application nicely integrates with his clinical expertise and will greatly facilitate his transition into an independent investigator. He will devote greater than 75 percent time to the proposed work. Research: The goals are to elucidate the molecular basis by which a novel neutrophil chemoattractant elicits important cell responses, processes which have direct relevance to GI mucosal pathobiology. A partially characterized phage, bearing peptide FGPNLTGRW (FGP), binds selectively to neutrophils (PMN) and monocytes, elicits calcium transients, and chemotaxis and degranulation in PMN. Preliminary data suggest that FGP initiates a novel G protein coupled signaling pathway and, among chemoattractant receptors on PMN, the receptor for FGP displays a novel requirement for ligand multivalency for activation. Studies are proposed to: 1) elucidate the most proximal signaling events in FGP activation of PMN to begin to systematically dissect this novel signaling; 2) to test the role of ligand valency in elicitation of cell responses by producing monomeric and multimeric FGP-bearing constructs for testing in PMN cell binding and response assays; and 3) to identify the receptor for FGP by biochemical/molecular methods given the novel nature of PMN activation by FGP and elimination of likely candidate receptors in preliminary studies. These studies have health relevance to inflammatory bowel diseases, mucosal infections, and other inflammatory disorders of mucosal surfaces. Environment: Dr. Jaye has been assigned laboratory space at Emory University Medical School in the Department of Pathology in the Epithelial Pathobiology Research Unit, adjacent to his sponsor?s, Dr. Parkos, and cosponsor?s, Dr. Madara, who will be primarily responsible for his scientific training. The facilities and resources available to him for his proposed work are outstanding. Furthermore, his sponsors, a panel of senior faculty consultants on campus and at other institutions will together foster his development and transition to a creative, independent researcher. He will also have access to a wealth of seminars in the scientific community at Emory University and formal didactic training within the Graduate School.
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