Affiliations: | | Biology Department | Amherst College, Amherst, MA, United States |
Area:
Drosophila NMJ
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High-probability grants
According to our matching algorithm, Ethan Graf is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2014 |
Graf, Ethan R |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Molecular Mechanisms of Active Zone Formation At Drosophila Synapses
DESCRIPTION (provided by applicant): Our long term goal is to identify the molecular mechanisms that control the formation and modulation of synapses. These mechanisms control the assembly of pre- and post- synaptic components required for proper synaptic function and ensure their appropriate apposition across the synaptic cleft. Regulation of such mechanisms controls synaptic plasticity and the processes that underlie the neural basis of learning and memory, and defects in these mechanisms are likely causes of neurodevelopmental and neurodegenerative disease. The Drosophila neuromuscular junction (NMJ) is a powerful model for studying synapse formation and function. Each NMJ is composed of hundreds of presynaptic release sites, or active zones, which are directly apposed to clusters of postsynaptic receptors in the muscle membrane. Proteins that compose the presynaptic release machine cluster at each presynaptic active zone to regulate efficient vesicle release. The mechanisms that control the accumulation of release machinery proteins at active zones remain unclear, but the protein Rab3 has recently been identified as playing a novel role that controls the localization of the presynaptic release machine to synapses. In the Drosophila rab3 mutant, the majority of release sites are devoid of presynaptic proteins required for efficient vesicle release. However the mechanism by which Rab3 controls the accumulation of release machinery proteins to active zones is unknown. In an RNAi screen to identify genes that interact with Rab3 to control active zone formation, three RNAi lines were identified that enhance or suppress the rab3 mutant phenotype. The proteins disrupted by these RNAi lines along with mutants of genes known to interact with Rab3 will be studied to determine the molecular mechanisms that control active zone development and synapse formation.
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