Role of Sec7 Domain Guanine Nucleotide Exchange Factors in Membrane Traffic

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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.