Establishing the 13-lined ground squirrel as a model for hibernation-inspired therapeutics

Project Summary Abstract Hibernating mammals have evolved to be able to endure extreme stresssub zero temperatures and lack of food for up toof the yearUnderstanding the genes and pathways involved in these adaptations would allow these mechanisms to be translated into human therapiesHoweverthe key animal model for hibernationthelined ground squirrelhas yet to be fully developedThe lack of a centralized platform is one major obstacle preventing gene based rational drug design from the protective effects of hibernationIn this proposalwe will build a multi omics hibernation discovery platform for thelined ground squirrel by integrating genomictranscriptomicproteomic and evolutionary analyses to generate novel drug targetsAs part of this workwe will produce the first ATAC seq study performed in a hibernating mammala key component of integrating genomic and transcriptomic dataas well as building networks to predict the function and regulation of predicted targetsWe will additionally perform in vitrovalidation of the predicted drug targets from our integrated analysesBy developing a discovery platform for a model hibernatorthelined ground squirreland demonstrating its utilitywe will enable therapeutic discovery for diseases with large clinical needs like heart diseasestrokeAlzheimer sType II Diabetesand sarcopeniaThis study is of interest to several NIH institutesNIDDKNHLBININDS and NIAMSProject Narrative Hibernating mammals represent an untapped resource for novel therapeutics development across many clinical indications including heart attackstrokeand diabetesHerewe propose to create an integrated computational platform for drug discovery using the hibernatinglined ground squirrel and perform functional validation of the identified therapeuticsThis work will be used to support drug development efforts relevant to multiple NIH institutes