The long-term goals of the Takahashi laboratory are to understand the molecular and genetic basis of circadian rhythms in mammals and to utilize forward genetic approaches in the mouse as a tool for gene discovery for complex behavior. In the five years, we have focused our attention in five areas: 1) identification of circadian clock genes and assignment of their function in the molecular mechanism of the circadian pacemaker; 2) analysis of central and peripheral circadian oscillators using real-time circadian reporters; 3) single-cell analysis of circadian oscillations using bioluminescence imaging methods; 4) in vivo analysis of circadian clock components using tissue-specific and conditional expression of circadian genes in mice; and, 5) identification of genes defined by mutations isolated in the large-scale mutagenesis screens we have conducted on neural and behavioral phenotypes.
RESEARCH INTERESTS
Molecular Neuroscience
Circadian Biology
Mouse Genetics and Genomics
Genetic Dissection of Behavior
Oscillator dynamics
RECENT PUBLICATIONS
Takahashi, J.S., K. Shimomura and V. Kumar, "Searching for genes underlying behavior: Lessons from circadian rhythms" Science, 322:909-912:3, 2008
Takahashi, J.S., H.-K. Hong, C.H. Ko and E.L. McDearmon, "The genetics of mammalian circadian order and disorder: Implications for physiology and disease" Nature Reviews Genetics, 9:764-775:11, 2008
Siepka, S.M., S.-H. Yoo, J. Park, W. Song, V. Kumar, Y. Hu, C. Lee and J.S. Takahashi, "Circadian mutant Overtime reveals F-box protein FBXL3 regulation of Cryptochrome and Period gene expression" Cell, 129:1011-1023:12, 2007
Liu, A.C. D.K. Welsh, C.H. Ko, H.G. Tran, E.E. Zhang, A.A. Priest, E.D. Buhr, O. Singer, K. Meeker, I.M. Verma, F.J. Doyle, J.S. Takahashi and S.A Kay, "Intercellular coupling confers robustness against mutations in the SCN circadian clock network" Cell, 129:605-616:11, 2005
McDearmon, E.L., K.N. Patel, C.H. Ko, J.A. Walisser, A.C. Schook, J.L. Chong, L.D. Wilsbacher, E-J Song, H-K Hong, C.A. Bradfield and J.S. Takahashi, "Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice" Science, 314:1304-1308:4, 2006
SIGNIFICANT PUBLICATIONS
Yoo, S.-H., S. Yamazaki, P.L. Lowrey, K. Shimomura, C.H. Ko, E.D. Buhr, S.M. Siepka, H.-K. Hong, W.-J. Oh, O.-J. Yoo, M. Menaker and J.S. Takahashi, "PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues." Proc Natl Acad Sci USA, 101:5339-5346:7, 2004
Lowrey, P.L., K. Shimomura, M.P. Antoch, S. Yamazaki, P.D. Zemenides, M.R. Ralph, M. Menaker and J.S. Takahashi., "Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau." Science, 288:483-491:8, 2000
Antoch, M.P., E.-J. Song, A.-M. Chang, M.H. Vitaterna, Y. Zhao, L.D. Wilsbacher, A.M. Sangoram, D.P. King, L.H. Pinto and J.S. Takahashi., "Functional identification of the mouse circadian Clock gene by transgenic BAC rescue." Cell, 89:655-667.:12, 1997
King, D.P., Y. Zhao, A.M. Sangoram, L.D. Wilsbacher, M. Tanaka, M.P. Antoch, T.D.L. Steeves, M.H. Vitaterna, J.M. Kornhauser, P.L. Lowrey, F.W. Turek and J.S. Takahashi., "Positional cloning of the mouse circadian Clock gene." Cell, 89:641-653.:12, 1997
Vitaterna, M.H., D.P. King, A.-M. Chang, J.M. Kornhauser, P.L. Lowrey, J.D. McDonald, W.F. Dove, L.H. Pinto, F.W. Turek and J.S. Takahashi., "Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior." Science, 264:719-725:6, 1994
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