AGING AND ADRENAL CATECHOLAMINE SYNTHESIS AND SECRETION

我提出了一个为期三年的职业发展计划，这将使我能够成功地过渡到进行最先进的、由外部资助的衰老研究。在菲利斯·M·怀斯博士的指导下，这项计划将包括与肯塔基大学老龄化领域的知名研究人员进行一系列强化培训。这次培训将使我在电生理学(与McMahon博士和Landfield博士合作)和分子生物学(与Wise博士和Estus博士合作)方面发展出高水平的专业知识，这两个领域我的经验相对较少，但这对于成功完成本申请中提出的研究以及未来老化特定项目的设计和执行都是至关重要的。此外，我还将与马特森博士一起接受激光共聚焦扫描显微镜方面的培训，这将极大地增强我目前在细胞内钙动态荧光成像方面的专业知识。在实验上，我将使用短期培养中的嗜铬细胞来检验这样的假设，即老年人肾上腺髓质儿茶酚胺分泌增加的速度是通过电压门控钙通道改变细胞内依赖尼古丁受体的钙信号增加的结果。从这些研究得出的数据将被纳入一份全面的RO1申请，该申请将在培训期结束时提交。我的长期职业目标是保持一个充满活力的、在全国和国际上受到尊重的老龄化研究计划。这份职业发展计划，再加上肯塔基大学丰富的与衰老相关的研究和学术资源，将使我能够实现这一目标。

A three-year career development plan is presented that will allow me to make a successful transition into conducting state-of the- art, extramurally funded aging research. With Dr. Phyllis M. Wise as my mentor, this plan will consist of a series of intensive training experiences with established investigators in the aging arena at the University of Kentucky. This training will allow me to develop a high level of expertise in electrophysiology (with Drs. McMahon and Landfield) and in molecular biology (with Drs. Wise and Estus), two areas in which I have relatively little experience, but which will be critical for both the successful completion of the studies proposed in this application as well as for the design and execution of future aging specific projects. In addition, I will receive training in confocal laser scanning microscopy with Dr. Mattson, which will dramatically enhance my current expertise in fluorescent imaging of intracellular Ca2+ dynamics. Experimentally, I will use chromaffin cells in short-term culture to test the hypothesis that the increased rate of adrenal medullary catecholamine secretion that occurs in aged subjects is the result of changes in nicotinic receptor-dependent increases in intracellular Ca2+ signaling via voltage-gated Ca2+ channels. The data derived from these studies will be incorporated into a comprehensive RO1 application that will be submitted toward the end of the training period. My long-term career objective is to maintain a vigorous, nationally and internationally respected research program in aging. This career development plan, coupled with the enormous wealth of aging-related research and academic resources that are available at the University of Kentucky, will allow me to achieve this objective.