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Genetic dissection of neuronal maintenance and demise

Abstract : Neurons live and function throughout the life of an organism. Hence, they face a distinct challenge of their maintenance and protection against cellular insults that accumulate during aging. I embarked on a systematic approach to understand mechanisms of neuronal maintenance and causes of neurodegeneration by bridging genetic studies in Drosophila with human Mendelian diseases. Through an unbiased genetic screen in Drosophila, I have identified 165 genes that are required for the development, function, and maintenance of the nervous system. We then, in collaboration with Baylor Hopkins Center for Mendelian Genomics, analyzed human homologs of these genes in human exomes from families with unsolved rare diseases. We identified disease-associated mutations in six families including the discovery of a novel disease linked gene ANKLE2. In parallel, the fly screen uncovered mutations in 32 genes that encode mitochondrial proteins. In my talk, I will discuss key findings of the genetic screen and elaborate on the molecular underpinnings that relate to neuronal demise due to mitochondrial impairments.