Molecular Mechanisms of Lysosome Biogenesis

溶酶体生物发生的分子机制

• 批准号: 1243037
• 负责人: Hanna Fares
• 金额: $ 63.11万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1243037&HistoricalAwards=false
• 关键词: Molecular; Mechanisms; Lysosome; Biogenesis

INTELLECTUAL MERITThe aim of this project is to decipher mechanisms of lysosome biogenesis. Lysosomes are the main membrane-bound, degradative organelles of eukaryotic cells. In addition to degrading endocytosed molecules from the extracellular medium, lysosomes regulate multiple essential cellular processes, including degrading material for turnover of cellular organelles, degrading material to respond to starvation, degrading signaling receptors to regulate developmental pathways, fusing with the plasma membrane to initiate wound healing, and mediating some cell death pathways. Given this central importance of lysosomes, it is striking that little is known about basic principles of how lysosomes are formed, the process of lysosome biogenesis. Fundamental to the understanding of how lysosome biogenesis is regulated requires identifying the proteins that function in this process. The aim of this project is to characterize six novel proteins that were identified as regulators of lysosome biogenesis. Using sophisticated genetic and cell biological tests in the C. elegans model system, this project will determine how these proteins interact to modulate the dynamic membrane events required to form a new lysosome. These approaches are likely to provide mechanistic molecular insight into lysosome biogenesis.BROADER IMPACTSFirst, this project will transform current views of membrane transport by establishing a molecular model of lysosome biogenesis. Second, this research program will continue to support a strong training mission in undergraduate student research. The P.I. has a strong record of undergraduate training, particularly with students from under-represented groups. The majority of these students eventually enter into graduate programs and pursue a career in science. Most of students that will be trained on the present project will be encouraged to present their work at research conferences and will be authors on peer-reviewed publications emerging from the work. This research program will serve as a platform for the scientific development of the next generations of scientists and health professionals.

智力优点该项目的目的是破译溶酶体生物发生的机制。 溶酶体是真核细胞的主要膜结合，降解细胞器。 除了从细胞外培养基中降解内养分分子外，溶酶体还调节多个必需的细胞过程，包括降解材料以使细胞器细胞器的转换材料，降解材料以响应饥饿，降解信号受体降解信号受体以调节plasmammabrane himbrane hind Pater hinter pation hint pation hint pation hinter pation patient patient patient pation nipain pation nipation somiation somiation somiation somiation somiatiation somiatiation somiatiation。 鉴于溶酶体的这一核心重要性，令人惊讶的是，关于溶酶体如何形成的基本原理，溶酶体生物发生的过程知之甚少。 对于理解如何调节溶酶体生物发生的基础，需要确定在此过程中起作用的蛋白质。 该项目的目的是表征六种被确定为溶酶体生物发生调节剂的新型蛋白质。 使用C. C.秀隐拉杆模型系统中的复杂遗传和细胞生物学测试，该项目将决定这些蛋白质如何相互作用以调节形成新的溶酶体所需的动态膜事件。 这些方法可能会提供对溶酶体生物发生的机械分子见解。BroaderTakeSfirst，该项目将通过建立溶酶体生物发生的分子模型来改变膜转运的当前观点。 其次，该研究计划将继续支持在本科生研究方面的强大培训任务。 P.I.具有丰富的本科培训记录，尤其是来自代表性不足小组的学生。 这些学生中的大多数最终从事研究生课程并从事科学职业。 将鼓励大多数将在本项目中接受培训的学生在研究会议上介绍他们的作品，并将成为从事工作中出现的同行评审出版物的作者。 该研究计划将成为下一代科学家和卫生专业人员科学发展的平台。