This research concerns daily biological clocks, which are an important component of the physiology of humans and other organisms. For example, medical and psychiatric studies have shown that these biological clocks are involved in some forms of depressive illness, """"""""jet lag,"""""""" drug tolerance/efficacy, memory, and insomnia. Therefore, understanding the biochemical mechanism of these clocks may lead to procedures which will be useful in the diagnosis and treatment of disorders which are relevant to sleep, mental health, and pharmacology. Despite the importance of clocked phenomena, however, the nature of the underlying biochemical mechanism is unknown. The research strategy is to study the molecular and genetic nature of biological clocks in two model organisms: one prokaryotic, and the other eukaryotic. The immediate aims of his research are (I) to manipulate genetically the model organisms so that they express rhythms which can be easily screened, (2) to identify and clone genes which are involved in the timing mechanism, (3) to characterize the input pathway (light) by which this clock is synchronized to environmental time, and (4) to track the output pathways of the clock """"""""upstream"""""""" to discover the clock mechanism itself. The long-term research goal is to understand the mechanism of this fascinating clockwork.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001179-09
Application #
6538239
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Asanuma, Chiiko
Project Start
1994-07-10
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
9
Fiscal Year
2002
Total Cost
$95,434
Indirect Cost
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
Shi, Shuqun; Hida, Akiko; McGuinness, Owen P et al. (2010) Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2. Curr Biol 20:316-21
Mittag, Maria; Kiaulehn, Stefanie; Johnson, Carl Hirschie (2005) The circadian clock in Chlamydomonas reinhardtii. What is it for? What is it similar to? Plant Physiol 137:399-409
Woelfle, Mark A; Ouyang, Yan; Phanvijhitsiri, Kittiporn et al. (2004) The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr Biol 14:1481-6
Izumo, Mariko; Johnson, Carl Hirschie; Yamazaki, Shin (2003) Circadian gene expression in mammalian fibroblasts revealed by real-time luminescence reporting: temperature compensation and damping. Proc Natl Acad Sci U S A 100:16089-94
Xu, Yao; Kanauchi, Akihito; von Arnim, Albrecht G et al. (2003) Bioluminescence resonance energy transfer: monitoring protein-protein interactions in living cells. Methods Enzymol 360:289-301
Xu, Yao; Mori, Tetsuya; Johnson, Carl Hirschie (2003) Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC. EMBO J 22:2117-26
Sai, Jiqing; Johnson, Carl Hirschie (2002) Dark-stimulated calcium ion fluxes in the chloroplast stroma and cytosol. Plant Cell 14:1279-91
Suzuki, Lena; Johnson, Carl Hirschie (2002) Photoperiodic control of germination in the unicell Chlamydomonas. Naturwissenschaften 89:214-20
Mori, Tetsuya; Saveliev, Sergei V; Xu, Yao et al. (2002) Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA. Proc Natl Acad Sci U S A 99:17203-8
Xu, Y; Johnson, C H (2001) A clock- and light-regulated gene that links the circadian oscillator to LHCB gene expression. Plant Cell 13:1411-25

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