|Title:||It’s a nonmodel world: hibernation "-omics" for basic research and drug discovery|
|Date:||Friday, 29 March 2019|
|Location:||Murie Life Science Bldg, Murie Auditorium.|
Hibernation is a highly dynamic phenotype that maximizes energy savings during periods of low resource availability. Additionally, because of their capability to tolerate physiological extremes, hibernators are exceptional models for identifying natural solutions to improve the human medical outcomes of a number of conditions. My talk will cover our work in both basic and translational aspects of hibernation research. In the first half, I will focus on our efforts to characterize the genetics underlying the seasonal onset of hibernation. When housed in an animal facility, 13-lined ground squirrels exhibit individual variation in the seasonal onset of hibernation, which is not explained by environmental or biological factors, such as body mass and sex. We hypothesized that underlying genetic factors instead drive variation in this timing. After increasing the 13-lined ground squirrel’s genome contiguity, we employed a genotype- by-sequencing approach to capture genetic variation in 153 13-lined ground squirrels. Combining this with datalogger records, we estimated high heritability for the seasonal onset of hibernation. Applying a genome-wide scan, we identified 2 loci significantly, and 12 loci suggestively, associated with hibernation onset. Finally, we used whole- genome sequencing and expression quantitative trait loci (eQTL) analyses in a subset of individuals to fine-map several of our top variants to putative causal loci. In the second half of my talk, I will present research from the company I recently co-founded, Fauna Bio, which is using hibernation “omics” data to guide discovery of novel human therapeutic targets. More specifically, we use weighted gene co-expression network analyses of 13-lined ground squirrel transcriptome data to identify key gene modules that recapitulate neuro- and cardioprotective phenotypes. We next perform in silico screens to detect compounds that produce the same gene module expression signatures in vitro. Finally, we validate our predictions by assessing the protective effects of these compounds in cell lines. My talk will highlight the power of applying a genetic mapping strategy to hibernation, as well as present a strategy to leverage hibernation “omics” data for human drug discovery.
Katharine Grabek is the chief science officer and co-founder of Fauna Bio, a seed-stage biotech company in Berkeley, CA, that focused on translating discoveries from animal genomics into human therapies. She recently completed her postdoctoral training in the Department of Biomedical Data Science at Stanford University. She is especially interested in understanding the evolutionary and genetic mechanisms that underlie mammalian hibernation. Her research has focused on utilizing proteomic, transcriptomic and genomic approaches to link the 13-lined ground squirrel’s genome to phenome.
Beginning in 1966 and continuing today, IAB hosts a weekly seminar for faculty, students, staff and the public during the academic year. The series attracts life scientists from Alaska and around the world.
If you wish to meet with a particular speaker, please contact one of the seminar coordinators or the IAB director's office at 907-474-7649.
The 2018-2019 faculty coordinators for this seminar series are Falk Huettmann and Cory Williams. Beginning in 2013, many of the seminars were recorded and can be viewed online. Speakers are listed in chronological order within academic years.
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