Molecular basis of cold tolerance

Yale University, New Haven CT

Investigators

Abstract

How do organisms sense and adapt to cold temperature? Cold tolerance, a special aspect of temperature sensitivity, is a key physiological capacity pertinent to all animals. Molecular mechanisms that contribute to the detection and modulation of cold sensitivity under normal and adaptive conditions are yet to be fully elucidated. This project aims to look at the general problem of cold sensitivity from a novel perspective - through studying cold-tolerant animals, thirteen-lined ground squirrels and Syrian hamsters. In addition to their ability to withstand deep cold during hibernation, squirrels and hamsters are cold tolerant even in the summer active state. This project seeks to understand the cellular and molecular basis of cold tolerance by performing a side-by-side comparison of physiological mechanisms in the squirrels, hamsters and mice. This research will highlight evolutionary changes that shaped cold tolerance and elucidate basic principles that underlie physiology of cold perception in vertebrates including humans. This project takes a multidiscplinary approach, involving behavioral paradigms, live-cell imaging, cell biology and in vitro biophysical analysis of ion channels to address this fundamental biological question. The PI will also run an innovative "Sensory Physiology Club" as a core outreach activity. The mission of the Club is to promote scientific education in human and animal physiology among school students from middle- and high schools. This activity will teach aspects of sensory biology and neural mechanisms underlying perception of sensory stimuli to school-aged children from Connecticut, New York and Massachusetts. An established collaboration with the Yale Pathways to Science and SCHOLAR programs, will serve to recruit participants and to monitor long-term impact of this program. The major goal of this study is to understand the molecular basis of cold sensitivity in mammalian hibernators, thirteen-lined ground squirrels and Syrian hamsters. A comparison of cold-sensitive and cold-tolerant animals will reveal anatomical, physiological, and genetic factors that support hibernation, a unique thermo-adaptive process. To investigate the abundance of temperature sensors in somatosensory system in active hibernators and compare it to mice, a non-hibernating species, histological analysis and live cell ratiometric calcium imaging of primary sensory neurons will be employed. It is known that Nav1.7 is a voltage-gated sodium channel responsible for initiation and propagation of action potential in somatosensory neurons. The proposal will test biophysical properties of squirrel and hamster Nav1.7 orthologues using electrophysiological recordings in heterologous cells and in neurons. Successful completion of this proposal will highlight molecular and cellular basis of cold tolerance and reveal a novel Nav1.7-mediated mechanism controlling cold temperature adaptations in mammalian hibernators. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.