From Genotype to Phenotype in Autism: The Role of Adaptive Physiology in Flies and Mice
- Speaker
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Graeme Davis, Ph.D.Morris Hertzstein Distinguished Professor of Medicine,
Department of Biochemistry and Biophysics,
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco
Simons Foundation Lectures are free public colloquia related to basic science and mathematics. These high-level talks are intended for professors, students, postdocs and business professionals, but interested people from the metropolitan area are welcome as well.
The identification of rare de novo mutations that confer high risk for autism spectrum disorders (ASD) has generated tremendous new molecular insight and progress. Yet, in cases where a known mutation confers risk, additional processes contribute to the phenotypic severity of ASD. A concept called homeostatic plasticity has garnered considerable attention as an adaptive process that might be relevant and contribute to the spectrum of ASD in the human population. But virtually nothing is known at a mechanistic level regarding the interface of homeostatic plasticity and ASD genetics. Furthermore, there remains ongoing debate whether homeostatic plasticity is normally induced or whether it is impaired by gene mutations that confer risk for ASD.
In this lecture, Graeme Davis will describe a novel, unexpected genetic architecture that connects mutations in ASD-associated genes with the mechanisms of homeostatic plasticity in both invertebrate and mammalian nervous systems. In particular, Davis will present a novel means by which a diversity of ASD-associated risk genes may converge to disrupt homeostatic plasticity, thereby compromising the robustness of synaptic transmission. This information may be relevant to new therapeutic approaches that might someday alleviate the phenotypic severity of ASD, regardless of the underlying genetic mutation(s) that confer risk for ASD.
About the Speaker
Davis received his B.A. at Williams College in 1989 and a Ph.D. from the University of Massachusetts in 1994. He pursued a postdoctoral fellowship at the University of California, Berkeley, under the guidance of Core S. Goodman. In 1998, he began his independent academic career as an assistant professor at the University of California, San Francisco, School of Medicine. Davis has remained at UCSF his entire career and is currently the Morris Hertzstein Distinguished Professor of Medicine and the former chairman of the department of biochemistry and biophysics. He and his laboratory have pioneered the field of homeostatic plasticity, beginning with work published in the mid-1990s and continuing to this day. They have taken advantage of genome-scale forward genetics screens in model organisms to define a majority of genes currently known to control the homeostatic regulation of neurotransmitter release and ion channel gene expression. Recently, the Davis lab has turned its attention to the interface of homeostatic plasticity and the mechanisms of neurological and psychiatric disease.