AGING AND OXIDATION IN SKELETAL AND CARDIAC MUSCLE

候选人的职业目标包括建立一个国际化的 公认的活性钙领域的独立研究计划 运输及其与衰老过程的关系。在同一时间， 应聘者有意成为某学院的正教授 机构。应聘者目前是某专业的助理教授 拥有良好的研究环境的州立大学 除了对教职员工要求的繁重的教学负担。虽然 她的实验室已经证明了它有能力进行一流的 研究，研究进展可能会因为过度的 非研究相关活动对考生时间和时间的要求 能量。设立独立科学家奖(ISA)将缓解这种情况 通过大幅减少候选人的教学和服务 将责任降到最低，以便让她专注于 研究活动并促进现有的和新的研究 在她研究生涯的这一关键时期的合作 发展。预计ISA将显著刺激 候选人的研究效率，因此对未来的竞争力 资金问题。 本研究旨在探讨主动行为的机制与调控。 两种动物肌浆网(SR)膜的钙转运 心脏和骨骼肌快速抽动，以及这一过程是如何受到影响的 通过生物体的老化。主要研究目标包括：(1)识别 对Ca-ATPase和SR脂质的氧化修饰的研究 将分离的SR囊泡暴露于活性氧物种，如果这些 模拟任何观察到的与年龄相关的变化；(2)定义 细胞环境在调节SR易感性中的作用 膜对氧化条件的影响；(3)与年龄相关的鉴定 修改，以及相关的结构和功能更改 肌肉中的Ca-ATPase和SR脂类；(4) 磷脂蛋白调节心肌钙离子的物理机制 ATPase，以及在衰老或氧化应激中这种变化是如何发生的。这些 目标将涉及一种综合的方法来检查生化 功能及其与蛋白质结构的关系 第三级和第四级。

The career goals of the candidate include building an internationally recognized independent research program in the area of active calcium transport and its relationship to the aging process. At the same time the candidate is interested in becoming a Full Professor at an academic institution. The candidate is currently an Assistant Professor at a major state university which has an excellent research environment with the exception of the heavy teaching load required of its faculty. Although her laboratory has demonstrated its ability to undertake first rate research, research progress is likely to be slowed by the excessive demands of non-research related activities on the candidate's time and energy. An Independent Scientist Award (ISA) would relieve this situation by substantially reducing the candidate's teaching and service responsibilities to a minimum in order to allow her to concentrate on research activities and to foster existing and new research collaborations during this crucial time in her research career development. The ISA is expected to significantly stimulate the candidate's research productivity and hence competitiveness for future funding. The proposed research addresses the mechanism and regulation of active calcium transport in sarcoplasmic reticulum (SR) membranes in both cardiac and fast twitch skeletal muscle, and how this process is affected by aging of the organism. Major research aims include: (1) identification of oxidative modifications to the Ca-ATPase and SR lipids initiated by exposure of isolated SR vesicles to reactive oxygen species, and if these simulate any of the observed age-related changes; (2) definition of the role of the cellular environment in modifying the susceptibility of SR membranes to oxidative conditions; (3) identification of age-related modifications, and associated structural and functional alterations of the Ca-ATPase and SR lipids in muscle; and (4) identification of the physical mechanism of phospholamban's regulation of the cardiac Ca- ATPase, and how this may be altered in aging or oxidative stress. These goals will involve an integrated approach to examining biochemical function and its relation to protein structure at the primary, secondary, tertiary and quartenary level.