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People / Graduate StudentsPatricia GoodwinPatricia.Goodwin@tufts.eduThesis Research Advisor: Peter Juo, Ph.D. My research focuses on cyclin-dependent kinase 5, a nervous-system specific kinase that has been shown to act pre- and postsynaptically as a regulator of neurotransmission and synaptic plasticity. I use the C. elegans neuromuscular junction as a model system to investigate how CDK-5 acts to regulate synaptic transmission in motor neurons. Primarily, I examine how CDK-5 acts to increase acetylcholine release by measuring behavioral responses of cdk-5 mutants to the acetylcholine esterase inhibitor aldicarb. Aldicarb causes acetylcholine to accumulate at the synapse, which leads to hypercontraction of the muscles and paralysis. The rate of paralysis depends on the amount of acetylcholine released from the motor neuron. Mutant worms lacking the cdk-5 gene paralyze more slowly than wild type worms and, conversely, worms that overexpress cdk-5 in their motor neurons paralyze more quickly than wild type worms. These results suggest that CDK-5 acts as a positive regulator of neurotransmitter release. To identify potential targets and regulators of CDK-5, I will perform an RNAi screen of 185 genes previously identified as players in synaptic transmission in cdk-5 mutants. Additionally, I will use fluorescently tagged synaptic proteins to study the effects of eliminating CDK-5 on the localization and abundance of synaptic components. |
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