The Systems Biology of Mammalian Puberty

哺乳动物青春期的系统生物学

• 批准号: 1121691
• 负责人: Sergio Ojeda
• 金额: $ 76万
• 依托单位: Oregon Health & Science University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121691&HistoricalAwards=false
• 关键词: Systems; Biology; Mammalian; Puberty

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.

在过去的几年里，研究人员观察到人类女性青春期的提前开始，这是一个令人担忧的趋势，因为青春期提前与癌症，肥胖，糖尿病和心血管疾病的风险增加有关。同样清楚的是，青春期的时间是由基因控制的，很可能是由一系列调节基因决定的。然而，很少有人试图确定控制哺乳动物发育中这一重要里程碑的遗传网络。Sergio Ojeda博士（神经科学家）和Kemal Sönmez（计算机/电气工程师）结合了专业知识，并在生物学和工程学之间建立了合作伙伴关系，以测试大脑内抑制基因网络控制女性青春期开始的假设。他们使用计算方法，系统生物学方法和分子策略的组合进行了初步研究，揭示了这种网络的存在，并表明它抑制了从属基因，如果不加以控制，将过早释放青春期过程。为了传播他们的发现，Ojeda和Sönmez将与西雅图的系统生物学研究所合作，建立一个基于网络的工具、链接和协议的数据库资源，用于通过互联网进行分析。 他们还将在其网站（www.example.com）上提供其原始数据、结果和代码，并将其数据和结果存款在公共数据库中。由于研究计划包括本科生和高中生的参与，该项目将鼓励年轻的研究人员使用类似的综合方法来研究哺乳动物系统中许多其他复杂的生理过程。这些研究将显著提高对哺乳动物青春期神经内分泌控制的基本系统机制的理解。