AGING AND ADRENAL CATECHOLAMINE SYNTHESIS AND SECRETION

我提出了一个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、外部资助的老龄化研究。在菲利斯·m·怀斯博士的指导下，这个计划将包括与肯塔基大学老年研究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方面发展出高水平的专业知识。McMahon和Landfield)和分子生物学(与dr。Wise和Estus)，我在这两个领域的经验相对较少，但这对于成功完成本申请中提出的研究以及未来老龄化特定项目的设计和执行都至关重要。此外，我将接受马特森博士的共聚焦激光扫描显微镜培训，这将极大地增强我目前在细胞内Ca2+动力学荧光成像方面的专业知识。在实验上，我将使用短期培养的嗜铬细胞来验证这样的假设，即老年受试者肾上腺髓质儿茶酚胺分泌速率的增加是由于烟碱受体依赖的细胞内Ca2+信号通过电压门控Ca2+通道增加的结果。从这些研究中获得的数据将纳入一份全面的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维持一个充满活力，在国内和国际上受到尊重的老龄化研究项目。这个职业发展计划，加上肯塔基大学大量与老龄化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.