User:Jesse D. Kirkpatrick/Notebook/Nikki and Jesse Research Proposal
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This project will focus on harnessing the power of bacteria to generate heat by turning on and off gene expression and ultimately overexpressing one of the uncoupling proteins involved in deregulating oxidative phosphorylation.
Members of the TRP family, specifically TRPM8 and TRPV4, regulate oxidative phosphorylation via uncoupling protein 1 (UCP1). TRPM8 positively regulates UCP1 and TRPV4 negatively regulates it via inhibition of PGC1-alpha. Uncoupling protein 1 is a major source of thermogenesis, and overexpression of this protein has provided hope for treating obesity and other metabolic conditions. However, the thermogenesis potential of this protein may itself be used as a local heating source, if overexpressed to an appropriate extent. We propose seeding bacteria in a cell and overexpressing UCP1 via TRPV4 inhibition and TRPM8 activation. We believe that this will increase heat production in bacteria, which can be used in a variety of applications.
TRPV4 negatively regulates UCP1 TRPM8 positively regulates UCP1
Project details and methods
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Increased thermogenesis by activation of UCP1
Bacteria TRPV4 shRNA
Ye et al. TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis.(2012) Cell Press.151(1): 96-110
Ma et al. Activation of the cold-sensing TRPM8 channel triggers UCPI-dependent thermogenesis and prevents obesity. (2012) Journal of Molecular Cell Biology. 4: 88-96
Hao et al. ADD1/SREBP1c activates the PGC1-α promoter in brown adipocytes (2010). Molecular and Cell Biology of Lipids. 1801(4): 421-429