Center for Genomic Experimentation and Computation

描述：(申请者提供)我们将建立一个结合 模拟原型信号的功能基因组和计算研究 转导途径。中心的工作将集中在“阿尔法计划”上。这个 这项工作的总体目标是获得预测动物行为的能力 在单个细胞水平上研究良好的生物调控系统。这个 系统是G蛋白受体偶联的信号转导途径 控制单倍体酿酒酵母对交配信息素的反应 因素。这条途径是监管网络的原型， 高等真核生物对外界刺激的反应。它也足以 易于处理，以促进众多功能基因组的开发 我们希望在这里实现的实验和计算方法； 并具有足够的聚集性，因此成功的实验和计算 战术可以迅速移植到其他有机体的其他系统中。 在项目期间，我们将：1)开发实验手段来测量 来自单个细胞和群体的系统输出和关键中间量 细胞的数量。2)开发计算方法来模拟细胞的行为和 大量的细胞。3)使用这些方法建立模型来预测 细胞随时间的定量行为以及对定义的 微扰。4)完成启发式目标，包括学习执行 把实验工作和学习结合起来，培养研究人员 多学科基因组研究环境。 中心的工作也将加深我们对重要但 -迄今知之甚少的科学问题，包括程度和 表观遗传变异的重要性，以及动态和 生物系统行为的数量方面受到控制。《中心》 将开发功能基因组和计算方法，可扩展到 系统大规模数据收集，适用于类似的 对包括人类在内的其他生物的研究。该中心将吸引和培训 在基因组研究中有大量的研究人员，他们中的许多人的背景是 物理、数学和其他非生物医学学科，世卫组织将继续 在这个纪律界面上工作。因此，该中心可以作为一个原型 对于随后的联合实验和计算实验室，努力 以了解基因组的功能。

DESCRIPTION: (provided by applicant) We will establish a center that combines functional genomic and computational research to model a prototype signal transduction pathway. Work at the center will focus on the "Alpha Project." The overall goal of the work is to gain the ability to predict the behavior of a well-studied biological regulatory system at the level of individual cells. The system is the G-protein receptor coupled signal transduction pathway that governs the response of haploid MATa S. cerevisiae to the mating pheromone, a factor. This pathway is a prototype for regulatory networks that govern response to external stimuli in higher eukaryotes. It is also sufficiently tractable to facilitate development of the numerous functional genomic experimental and computational methods that we hope to bring into being here; and sufficiently paradigmatic so that successful experimental and computational tactics can be ported rapidly to other systems in other organisms. During the project period, we will: 1) Develop experimental means to measure system output and key intermediate quantities from single cells and populations of cells. 2) Develop computational means to simulate the behavior of cells and populations of cells. 3) Use these methods to build models that predict the quantitative behavior of cells over time and in response to defined perturbations. 4) Accomplish heuristic goals including learning to perform combined experimental work and learning to develop investigators in a multidisciplinary genomic research environment. Work at the Center will also deepen our understanding of important but so-far-poorly understood scientific questions, including the extent and importance of epigenetic variation, and the means by which dynamic and quantitative aspects of biological system behavior are controlled. The Center will develop functional genomic and computational methods that are scalable to systematic large-scale data collection and that are applicable to similar studies of other organisms, including humans. The Center will attract and train in genomic research numbers of researchers, many of whose backgrounds are in physics, mathematics, and other nonbiomedical disciplines, who will continue to work at this disciplinary interface. The center may thus serve as a prototype for subsequent combined experimental and computational laboratories that strive to understand genome function.