Understanding the limits of human heat tolerance from the cell to the whole-body response

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Temperature regulation is a vital aspect of human survival. However, exercise and/or exposure to hot environments can lead to dangerous increases in body temperature. To offset this increase, highly developed autonomic thermoeffector responses (cutaneous vasodilation and sweating) are activated to facilitate whole-body heat loss during heat stress. Using the world's only air calorimetry (a device that provides a very precise measurement of the heat dissipated by the human body), we showed that physiological control of thermoeffector responses and therefore whole-body heat loss can vary as a function of several inter-individual factors (e.g., age, sex, other) and intra--individual factors (e.g., fitness, hydration, exposure duration). This includes the influence of non-thermal factors associated with the activation of sensory receptors (e.g., baroreceptors, metaboreceptors). While our calorimetry-based research has advanced our understanding of the factors limiting human heat tolerance, our emerging work evaluating the cellular heat stress response is uncovering the complex cellular mechanisms that contribute to heat-related vulnerabilities. To continue advancing this important work, I am seeking to replace older, inadequate instruments and obtain new tools to increase our capacity to conduct this innovative research and maximize our research output. Specifically, the aim of this proposal is to expand the scope and impact of our research activities by replacing our calorimeter's antiquated data acquisition interface platform for the monitoring of physiological responses (i.e., scalable system enabling the addition of a data acquisition system capable of accommodating a range of hardware interfaces needed to record multiple physiological variables under one system). This would eliminate our dependence on multiple monitoring stations employing different data acquisition systems and software platforms and provide capacity for future expansion for the monitoring of other physiological variables in our calorimetry-based studies. Further, we are seeking to replace older tools and acquire newer instruments (e.g., centrifuge, platform rocker, waving rotator, Western blot imaging system, Western blot electrophoresis system) to meet our needs and enhance our capacity to evaluate protein and gene responses to study the cellular mechanisms underlying heat vulnerabilities. This would allow us to bridge the gap in our understanding of the factors mediating human heat tolerance from the cell to the whole-body response, helping us achieve the next echelon of discovery and innovation. Importantly, it will attract a new cadre of trainees and drive a new generation and culture of scientific growth to address real-world challenges faced by industry and other sectors of our population affected by extreme heat spurred by a warming planet.