Genetic analysis of AMPK function in Drosophila

果蝇AMPK功能的遗传分析

• 批准号: 7107225
• 负责人: Michelle L Bland
• 金额: $ 4.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107225
• 关键词: Drosophilidae; adenosine monophosphate; arthropod genetics; bioenergetics; biological signal transduction; enzyme activity; enzyme mechanism; gene mutation; genetic enhancer element; genetic regulation; genetic screening; postdoctoral investigator; serine threonine protein kinase

DESCRIPTION (provided by applicant): Eukaryotes tolerate fluctuations in the environmental supply of nutrients and their consumption by cellular metabolism by suspending anabolic processes and utilizing stored energy. From yeast to mammals, the AMP-activated kinase (AMPK) serves as the sensor of cellular energy stores and the activator of metabolic switches that conserve ATP. While the key role of AMPK in directing cellular metabolism is well established, little is known about the upstream regulators and downstream effectors of AMPK signaling. The goal of these studies is to use a genetic approach in Drosophila to identify novel components of the AMPK signaling pathway. In specific aim 1, I will determine the growth and metabolic phenotypes resulting from loss- and gain-of-function of AMPK. In specific aim 2, I will perform genetic and biochemical analyses to confirm relationships between AMPK and its putative upstream regulators and downstream substrates. In specific aim 3, I will undertake a genetic screen for suppressors and enhancers of AMPK mutant phenotypes to discover novel components of the AMPK signaling pathway. Collectively, these studies should shed light on an important pathway that has resisted characterization using biochemical approaches.

描述（由申请人提供）：真核生物通过暂停合成代谢过程和利用储存的能量来耐受环境营养物供应的波动以及细胞代谢对营养物的消耗。从酵母到哺乳动物，AMP 激活激酶 (AMPK) 充当细胞能量储存的传感器和保存 ATP 的代谢开关的激活剂。虽然 AMPK 在指导细胞代谢中的关键作用已得到充分证实，但人们对 AMPK 信号传导的上游调节器和下游效应器知之甚少。这些研究的目标是在果蝇中使用遗传方法来鉴定 AMPK 信号通路的新成分。在具体目标 1 中，我将确定 AMPK 功能丧失和获得所导致的生长和代谢表型。在具体目标 2 中，我将进行遗传和生化分析，以确认 AMPK 与其假定的上游调节因子和下游底物之间的关系。在具体目标 3 中，我将对 AMPK 突变表型的抑制子和增强子进行遗传筛选，以发现 AMPK 信号通路的新组件。总的来说，这些研究应该揭示一个无法使用生化方法进行表征的重要途径。