All forms of life, ranging from bacteria to humans, are intimately affected by ambient temperature which constantly fluctuates. To survive and thrive, animals and humans have evolved sensory systems, which comprise thermosensory neurons/circuits and molecular thermal sensors to detect, respond, and adapt to temperature changes in the environment. Defects in temperature perception lead to neurological and metabolic disorders. Research in the past two decades has led to an increasingly clear understanding of how animals sense heat, including the identification of various types of heat-sensitive neurons/circuits and channels/receptors in diverse organisms ranging from worms to mammals, which reveals a remarkable conservation in the mechanisms of thermosensation. By contrast, much less is known about how animals sense cold temperatures. Here, using state-of-the-art thermoelectric technologies, we have developed novel thermoelectric devices to rapidly and precisely change ambient temperature. By taking advantage of this technological advance, we propose to investigate the neural and genetic basis of cold sensation in C. elegans, a popular genetic model organism widely used for the study of sensory perception. To do so, we will use a multidisciplinary approach combining behavioral, genetic, calcium imaging, and electrophysiological analyses. As thermosensory mechanisms particularly those involving thermosensitive channels/receptors tend to be evolutionarily conserved, our work will provide novel insights into the mechanisms underlying cold sensation in mammals and related neurological and metabolic disorders.

Public Health Relevance

Defects in temperature perception lead to neurological diseases such as chronic pain syndromes, as well as metabolic disorders such as diabetes and obesity. The proposed work will facilitate our understanding of thermosensation in humans and how its defects lead to those neurological and metabolic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM083241-09
Application #
9385037
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Sesma, Michael A
Project Start
2008-05-05
Project End
2018-07-31
Budget Start
2017-09-11
Budget End
2018-07-31
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Jun, Heejin; Yu, Hui; Gong, Jianke et al. (2018) An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling. Nat Med 24:814-822
Rauthan, Manish; Gong, Jianke; Liu, Jinzhi et al. (2017) MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans. Cell Rep 21:1434-1441
Wang, Xiang; Li, Guang; Liu, Jie et al. (2016) TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons. Neuron 91:146-54
Wescott, Seth A; Ronan, Elizabeth A; Xu, X Z Shawn (2016) Insulin signaling genes modulate nicotine-induced behavioral responses in Caenorhabditis elegans. Behav Pharmacol 27:44-9
Gong, Jianke; Yuan, Yiyuan; Ward, Alex et al. (2016) The C. elegans Taste Receptor Homolog LITE-1 Is a Photoreceptor. Cell 167:1252-1263.e10
Li, Zhaoyu; Iliff, Adam J; Xu, X Z Shawn (2016) An Elegant Circuit for Balancing Risk and Reward. Neuron 92:933-935
Chaudhuri, Jyotiska; Bose, Neelanjan; Gong, Jianke et al. (2016) A Caenorhabditis elegans Model Elucidates a Conserved Role for TRPA1-Nrf Signaling in Reactive ?-Dicarbonyl Detoxification. Curr Biol 26:3014-3025
Li, Guang; Gong, Jianke; Lei, Haoyun et al. (2016) Promotion of behavior and neuronal function by reactive oxygen species in C. elegans. Nat Commun 7:13234
Xiao, Rui; Chun, Lei; Ronan, Elizabeth A et al. (2015) RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior, and Aging in C. elegans. Cell Rep 11:1123-33

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