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Hiroki R. Ueda
M.D., Ph.D.
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Recent large-scale efforts in genome-sequencing and expression analysis have produced an embarrassment of riches for life science researchers ? biological data can now be accessed in quantities that are orders of magnitude greater than were available even a few years ago. Now, the growing need for integration of data sets has set the stage for the advent of systems biology, in which discrete biological processes and phenomena are approached as complex, interactive systems. We see systems biology research as a multi-stage process, beginning with the identification and analysis of individual system components and their networked interactions, and leading to the ability to control existing systems and design new ones based on an understanding of structure and underlying principles.
Our lab takes the mammalian circadian clock as a relatively simple and self-contained initial model for the study of a biological system. In addition to its advantages as a basic research model, the function of the circadian clock is intimately involved in the control of metabolic and hormonal cycles, and its dysregulation is linked to the onset and symptomatology of numerous human diseases, including sleep disorders. An improved understanding at the system level promises to provide biomedical and clinical investigators with a powerful new arsenal to attack these conditions.
To address complex and dynamic biological systems such as the circadian clock, it is necessary to make comprehensive and precise measurements of the system's dynamics and to work out the organization of its underlying gene network. Our team previously conducted a genome-wide screen and statistical analysis of gene expression to identify the clock-controlled genes that are rhythmically expressed in the central (suprachiasmatic nucleus; SCN) and peripheral (liver) circadian clocks. Analysis of the transcriptional regulation of gene expression in the morning, daytime, evening and night periods revealed a gene network of inter-regulating activators and inhibitors of time-linked gene expression. Our recent work has further demonstrated a number of general design principles underlying the transcriptional dynamics of clock-related genes. We next hope to apply these findings to the study of more involved and elaborate developmental processes.
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