The Systems Biology of Mammalian Puberty

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During the last several years, investigators have observed an earlier initiation of human female puberty, a worrisome trend because early puberty is associated with increased risk for cancer, obesity, diabetes, and cardiovascular disease. It has also become clear that the timing of puberty is under genetic control, and likely determined by a host of regulatory genes. Yet, few attempts have been made to identify the genetic networks controlling this critical milestone in mammalian development. Drs. Sergio Ojeda (a neuroscientist) and Kemal Sönmez (a computer/electrical engineer) have combined expertise and developed a partnership between biology and engineering to test the hypothesis that a repressive gene network operating within the brain controls the initiation of female puberty. Using a combination of computational methods, systems biology approaches and molecular strategies, they performed preliminary studies revealing the existence of such a network and showing that it represses subordinate genes, which if left unchecked, would unleash the pubertal process prematurely. To disseminate their findings, Ojeda and Sönmez will partner with the Institute for Systems Biology in Seattle to generate a database resource of Web-based tools, links and protocols for analyses accessible via Internet. They will also make their raw data, results, and codes available on their website (www.sonmezsysbio.org), and deposit their data and results in public databases. Because the research plan includes the participation of undergraduate students and high-school students, The project will encourage young investigators to use similar integrative approaches for the study of many other complex physiological processes in mammalian systems. Theses studies will significantly enhance the understanding of basic systems-wide mechanisms underlying the neuroendocrine control of mammalian puberty.