Role of Sec7 Domain Guanine Nucleotide Exchange Factors in Membrane Traffic

智力价值膜运输调节蛋白质和脂类的分泌和向细胞内细胞器和质膜的输送。调控这一过程的机制在所有真核生物中基本上是保守的，在一个物种中学到的东西可以揭示在其他物种(包括人类)中发生的事件。在单细胞生物中，膜运输维持细胞生长和与环境的相互作用。在多细胞生物体中，细胞外基质的沉积和细胞黏附、生长因子和营养物质的释放和摄取以及环境感知受体和信号转导的插入都需要膜运输，即整合组织和器官的发育和生理反应的所有过程。该项目将重点研究膜交通的关键调节因子ADP-核糖化因子(ARF)GTP酶。具体地说，促进ARF激活的机制和分子将被识别和表征。该项目研究调节膜运输的分子机制，以了解细胞和有机体生命所必需的过程。该项目的更广泛影响是：(1)在尖端分子、成像、生化和基因技术方面对博士后研究员、研究生和本科生进行培训和指导，以探索细胞生理学的关键问题。(2)通过积极招募和指导代表不足的群体进入科学职业生涯，促进科学公平。(3)通过与结构和生物物理学科学家交流，促进跨学科协同作用，提供更多跨领域的技术和想法。(4)通过向世界各地的实验室开发和传播质粒、抗体、重组蛋白和实验方法，促进全球科学基础设施。该项目具有额外的社会效益，因为它将提供下一代学术研究人员和教师，提高美国科学企业的竞争力，并为科学和教育领域的非学术工作培养训练有素的个人。

Intellectual MeritMembrane traffic mediates secretion and the delivery of proteins and lipids to intracellular organelles and the plasma membrane. The mechanisms regulating this process are largely conserved throughout all eukaryotes and what is learned in one species can reveal events occurring in other species (including humans). In unicellular organisms, membrane traffic sustains cell growth and interactions with the environment. In multicellular organisms, membrane traffic is required for deposition of the extracellular matrix and cell adhesion, the release and uptake of growth factors and nutrients, and the insertion of environment sensing receptor and signal transducers, i.e., all the processes that integrate the developmental and physiological responses of tissues and organs. This project will focus on key regulators of membrane traffic, the ADP-ribosylation factor (ARF) GTPases. Specifically, the mechanisms and molecules that facilitate ARF activation will be identified and characterized. This project studies the molecular mechanisms that regulate membrane trafficking to understand a process essential for cellular and organismal life.Broader ImpactsThe broader impacts of this project are: (1) Training and mentoring of postdoctoral fellows, graduate students and undergraduates in cutting-edge molecular, imaging, biochemical and genetic technologies to probe key questions in cellular physiology. (2) Promoting scientific equity by actively recruiting and mentoring under-represented groups to enter scientific careers. (3) Promoting interdisciplinary synergy by interfacing with structural and biophysical scientists to provide additional cross-field fertilization of technologies and ideas. (4) Promoting global scientific infrastructure by developing and disseminating plasmids, antibodies, recombinant proteins and experimental approaches to labs worldwide. This project has additional societal benefits because it will provide the next generation of academic researchers and teachers, improve the competitiveness of US scientific enterprise and prepare highly trained individuals for non-academic jobs in science and education.