Project Summary/Abstract
Hibernating mammals have evolved to be able to endure extreme stress, sub-zero temperatures
and lack of food for up to 75% of the year. Understanding the genes and pathways involved in
these adaptations would allow these mechanisms to be translated into human therapies.
However, the key animal model for hibernation, the 13-lined ground squirrel, has yet to be fully
developed. The lack of a centralized platform is one major obstacle preventing gene-based
rational drug design from the protective effects of hibernation. In this proposal, we will build a
multi-omics hibernation discovery platform for the 13-lined ground squirrel by integrating
genomic, transcriptomic, proteomic and evolutionary analyses to generate novel drug targets.
As part of this work, we will produce the first ATAC-seq study performed in a hibernating
mammal, a key component of integrating genomic and transcriptomic data, as well as building
networks to predict the function and regulation of predicted targets. We will additionally perform
in-vitro¿ validation of the predicted drug targets from our integrated analyses. By developing a
discovery platform for a model hibernator, the 13-lined ground squirrel, and demonstrating its
utility, we will enable therapeutic discovery for diseases with large clinical needs like heart
disease, stroke, Alzheimer’s, Type II Diabetes, and sarcopenia. This study is of interest to
several NIH institutes (NIDDK, NHLBI, NINDS and NIAMS).