CAREER: Molecular and Genetic Analysis of Synaptic Vesicle Recycling

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IBN-0093170ZHANGCognitive functions of the nervous system depend largely on the integrity of neuronal communication. This process includes the release of neurotransmitter from synaptic vesicles, activation of postsynaptic receptors, and recycling of synaptic vesicles. The recycling step is crucial for continuous synaptic transmission. However, our understanding of vesicle recycling and its regulation remains rudimentary. Dr. Zhang will exploit the power of genetics, molecular biology, and electrophysiology in the fruitfly Drosophila to investigate the molecular mechanisms underlying vesicle recycling. Recently, Dr. Zhang and his colleagues revealed that clathrin-mediated endocytosis, a major vesicle recycling pathway, is tightly regulated by LAP (like-AP180), a putative fly homolog of the mammalian clathrin assembly protein AP180. Dr. Zhang will test whether LAP is a functional homolog of AP180 and determine precisely how LAP regulates vesicle reformation. He will also identify structural motifs critical for clathrin coat assembly and determine their roles in synaptic transmission. The results from these studies have broad biological and clinical significance because clathrin is commonly used for endocytosis and intracellular protein trafficking. Dr. Zhang's research is also closely integrated with training of students and outreach to local schools. He will develop new curriculum for both undergraduates and graduates at his University. He will also expand an on-going annual workshop to familiarize local elementary and high students and their teachers with basic neurobiological research. Through these education and outreach efforts, Dr. Zhang hopes to inspire more young students to pursue careers in biological research and education. This CAREER award will not only advance our understanding of synaptic transmission, but also help develop programs benefiting future neurobiologists.