Training Underrepresented Basic Science Researchers Utilizing Structure-Function Investigations of Neuropeptide Receptors

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Principal Investigator: James E. PorterProposal #: 0235146Title of Proposal: Training Underrepresented Basic Science Researchers Utilizing Structure-Function Investigations of Neuropeptide ReceptorsAbstract: The immediate goal of this project is to promote the teaching and training of students by characterizing fundamental processes by which a stimulus is detected and transmitted by organisms to initiate essential biological events. The calcitonin gene-related peptide (CGRP) is an established neurotransmitter that is prominently associated with initiating complex multicellular interactions that regulate or modulate the function of many living organisms (e.g., sensory pathways). Unfortunately, the types of CGRP ligands currently available limit information about the cellular effects associated with CGRP modulation of physiological responses. This proposal will test the hypothesis that insights into the cellular mechanisms of CGRP mediated effects will provide a background for the rational development of novel non-peptide ligands. Pharmacological analysis of CGRP signaling mechanisms for mutant and wild type proteins will be examined using biochemical, molecular and cell biological techniques. Differences in the properties of these mutant proteins from the wild type will be used to advance a molecular model associated with CGRP cellular effects. Furthermore, this knowledge could be used to develop compounds that would help researchers understand the specific modulatory functions associated with this neuropeptide. Moreover, results generated from completion of this proposal will forward our understanding of how ubiquitous peptides are recognized and communicated through sensory pathways using intracellular signaling systems. Finally, this research would benefit the education and training of underrepresented groups in a demographically disadvantaged state, by providing support for advanced training in the biological sciences.