Laboratory for Systems Biology
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Activities

Summary of Research Achievement in LSB
For the last five years, LSB has aimed to establish a range of systems-biological approaches. For each stage of systems-biological research, we have successfully developed new strategies and technologies for genome-wide profiling and bioinformatics (for System Identification), quantitative measurement (for System Analysis), quantitative perturbation of cellular state (for System Control), and implementation of artificial circuits in cells (for System Design). We have applied these systems-biological approaches to specific system-level questions involving the mammalian circadian clock, which LSB took as an initial model system, and this has lead to a number of new discoveries, including the identification of mammalian and fly clock circuits (Ueda H.R. et al, 2005, Nature Genetics, Matsumoto A., Ukai-Tadenuma M., Yamada R.G. et al, 2007, Genes & Development); the pivotal role of feedback repression in mammalian circadian clocks (Sato T.K., Yamada R.G., Ukai H. et al, 2006, Nature Genetics); desynchronization as the underlying mechanism for singularity behaviors of mammalian circadian clocks (Ukai H., Kobayashi T.J. et al, Nature Cell Biology, 2007); and the design principle of clock-controlled elements and circadian transcriptional outputs (Kumaki Y. et al, submitted, and Ukai-Tadenuma M., Kasukawa T. et al, submitted). Interdisciplinary interactions in LSB have produced a range of unexpected discoveries and inventions as byproducts of the laboratory's main research activities, including the discovery of general principles involved in gene expression dynamics and metabolic network evolution (Ueda H.R. et al, 2004a, PNAS, and Ueda H.R. et al, submitted). This is in addition to the invention of new diagnostic methods to detect internal body-time from the interaction between genomics and statistics (Ueda H.R. et al, 2004b, PNAS). LSB also appreciates that the seamless integration of computation/theory and experiments will facilitate the establishment of such systems-biological approaches. During the last five years, LSB has recruited researchers, technical staff and students from diverse scientific and/or technological backgrounds, including molecular and cellular biology, genomics, biochemistry, bioimaging, bioinformatics, physics, and applied mathematics. This has allowed the LSB to be established as a stable platform for laboratory members to carry out interdisciplinary collaboration with each other, and thereby incubate new concepts and technologies.
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