Circadian (daily) rhythms are a crucial component of human health. Inappropriate daily regulation/phasing of sleep and other clock-controlled parameters is associated with several types of depression, obesity/metabolic syndrome, and cardiovascular disease. At the cellular level, circadian pacemakers regulate cell division, metabolism, and gene expression networks. The selective pressures that led to the evolution of the special characteristics of circadian rhythms (esp. their precise 24 h time constant and temperature compensation) have not been identified. How can metabolic processes that intrinsically feed back with short time constants be recruited by selective pressures to the establishment of a self-sustained 24 h oscillator that is temperature compensated? The answer to this question has broad significance to our understanding of cell cycles, gene transcriptional networks, "Systems" biology, evolutionary processes, and chronobiology. This project will undertake an experimental evolution of biological rhythms that have circadian characteristics in a quest to identify relevant selective pressures and whether particular metabolic pathways are predisposed towards the evolution of self-sustained biological oscillators. Single cell organisms with genetic capabilities will be subjected to a variety of environmental cycles (light/dark, UV- B, temperature) to ascertain which conditions can lead to the evolution of biological oscillators with circadian characteristics. The successful evolution of such oscillators will be assessed with luminescence reporters of cell cycle and metabolic events.

Public Health Relevance

RELEVANCE TO PUBLIC HEALTH: Circadian rhythms organize the temporal activities of metabolism and gene expression;disruption of these daily programs has serious consequences for human health and well-being. Identifying the selective pressures that can shape metabolism to establish biological clocks will enable the understanding of the history whereby clock mechanisms were developed and how clocks are coupled to metabolism. Ultimately, knowing these links may help to provide therapies for diseases that are related to clock disruption.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM088595-04
Application #
8307002
Study Section
Special Emphasis Panel (ZGM1-CBB-7 (EU))
Program Officer
Sesma, Michael A
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$305,791
Indirect Cost
$109,771
Name
Vanderbilt University Medical Center
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Egli, Martin; Johnson, Carl H (2015) Biochemistry that times the day. Biochemistry 54:104-9
Shi, Shu-qun; Bichell, Terry Jo; Ihrie, Rebecca A et al. (2015) Ube3a imprinting impairs circadian robustness in Angelman syndrome models. Curr Biol 25:537-45
Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie (2015) Circadian Clocks: Unexpected Biochemical Cogs. Curr Biol 25:R842-4
Qin, Ximing; Mori, Tetsuya; Zhang, Yunfei et al. (2015) PER2 Differentially Regulates Clock Phosphorylation versus Transcription by Reciprocal Switching of CK1ε Activity. J Biol Rhythms 30:206-16
Pattanayek, Rekha; Xu, Yao; Lamichhane, Aashish et al. (2014) An arginine tetrad as mediator of input-dependent and input-independent ATPases in the clock protein KaiC. Acta Crystallogr D Biol Crystallogr 70:1375-90
Johnson, Carl Hirschie; Egli, Martin (2014) Metabolic compensation and circadian resilience in prokaryotic cyanobacteria. Annu Rev Biochem 83:221-47
Xu, Yao; Ma, Peijun; Shah, Premal et al. (2013) Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature 495:116-20
Robertson, James Brian; Davis, Chris R; Johnson, Carl Hirschie (2013) Visible light alters yeast metabolic rhythms by inhibiting respiration. Proc Natl Acad Sci U S A 110:21130-5
de la Iglesia, Horacio O; Johnson, Carl Hirschie (2013) Biological clocks: riding the tides. Curr Biol 23:R921-3

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