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

首席研究员：James E.搬运工提案编号：0235146提案标题：利用神经肽受体的结构-功能研究培训代表性不足的基础科学研究人员摘要：该项目的直接目标是通过表征生物体检测和传输刺激以启动基本生物事件的基本过程来促进学生的教学和培训。 降钙素基因相关肽（CGRP）是一种已确立的神经递质，其与启动复杂的多细胞相互作用显著相关，所述多细胞相互作用调节或调节许多活生物体的功能（例如，感觉通路）。 不幸的是，目前可用的CGRP配体的类型限制了关于与生理反应的CGRP调节相关的细胞效应的信息。 这项建议将测试的假设，深入了解CGRP介导的作用的细胞机制将提供一个新的非肽配体的合理发展的背景。 将使用生物化学、分子和细胞生物学技术对突变型和野生型蛋白质的CGRP信号传导机制进行药理学分析。 这些突变蛋白质与野生型的性质差异将用于推进与CGRP细胞效应相关的分子模型。 此外，这些知识可以用于开发化合物，帮助研究人员了解与这种神经肽相关的特定调节功能。 此外，从完成这项建议产生的结果将推进我们的理解，无处不在的肽是如何识别和沟通，通过感觉通路使用细胞内信号系统。 最后，这项研究将通过为生物科学的高级培训提供支持，有益于在人口统计学上处于不利地位的国家中代表性不足的群体的教育和培训。

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.