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Systems Biology
Hiroki R. Ueda
M.D., Ph.D.

Recent large-scale efforts in genome-sequencing, expression profiling and functional screening have produced an embarrassment of riches for life science researchers and biological data can now be accessed in quantities that are orders of magnitude greater than were available even a few years ago. The growing need for interpretation of data sets, as well as the accelerating demand for their integration to a higher level understanding of life, has set the stage for the advent of systems biology, in which biological processes and phenomena are approached as complex and dynamic systems. Systems Biology is a natural extension of molecular biology, and can be defined as "biology after the identification of key genes." We see systems-biological research as a multi-stage process, beginning with the comprehensive identification and quantitative analysis of individual system components and their networked interactions, and leading to the ability to drive existing systems toward a desired state and design new ones based on an understanding of structure and underlying principles.

Over the last several years, the Laboratory for Systems Biology (LSB) has worked to establish experimental systems biology at the molecular-to-cellular level and apply them to system-level questions of complex and dynamic biological systems, such as the mammalian circadian clock. In October 2009, our laboratory was re-designated as a Project Lab in the Center Directorfs Strategic Program for Systems Biology research to promote challenging research endeavors. Based on the achievements over the past years, we strongly feel that it is now the time for us to take the next step forward toward experimental systems biology at the cellular-to-organism level.

Over the next several years, we intend to develop an efficient experimental platform to identify, monitor, and perturb cellular networks within organism. To this aim, we will attempt to invent and combine several key technologies ranging from (i) rapid engineering of the genome of ES cells, (ii) generation of g100% chimerah animals for F0 phenotyping, and (iii) phenotype analysis of a small number of the generated animals (ideally with a single animal). Full utilization of these technologies will formulate cellular-to-organism-level systems biology, which will provide new strategies and concepts for the diagnosis, treatment, and prevention of biological-time-related disorders, including rhythm disorder, seasonal affective disorder, and sleep disorder.

Select references

Tsujino K, et al. Establishment of TSH real-time monitoring system in mammalian photoperiodism. Genes Cells 18.575-88 (2013)

Sunagawa G. A, et al. FASTER: an unsupervised fully automated sleep staging method for mice. Genes Cells (2013)

Jolley C. C, et al. A design principle for a posttranslational biochemical oscillator. Cell Rep 2.938-50 (2012)

Ukai-Tadenuma M, et al. Delay in feedback repression by cryptochrome 1 is required for circadian clock function. Cell 144.268-81 (2011)

Masumoto K. H, et al. Acute induction of Eya3 by late-night light stimulation triggers TSHbeta expression in photoperiodism. Curr Biol 20.2199-206 (2010)

Isojima Y, et al. CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc Natl Acad Sci U S A 106. 15744-9 (2009)