Center for Genomic Experimentation and Computation

描述：（由申请人提供）我们将建立一个中心， 功能基因组学和计算研究来模拟原型信号 转导途径该中心的工作将集中在"阿尔法项目"上。"那 工作的总体目标是获得预测行为的能力， 在单个细胞水平上的生物调节系统得到充分研究。的 系统是G蛋白受体偶联的信号转导通路， 控制单倍体MATa S的反应。酿酒酵母交配信息素， 因子这条途径是一个监管网络的原型， 高等真核生物对外界刺激的反应。也足以 易于处理以促进许多功能性基因组的开发， 实验和计算方法，我们希望在这里实现; 并且足够的典型性，使得成功的实验和计算 策略可以迅速移植到其他生物的其他系统中。 在项目期间，我们将：1）开发实验手段来测量 来自单细胞和群体的系统输出和关键中间量 信元2)开发计算方法来模拟细胞的行为， 细胞群。3)使用这些方法来构建预测 细胞随时间的定量行为和对定义的 扰动4)完成启发式目标，包括学习如何执行 结合实验工作和学习，以培养调查人员在一个 多学科基因组研究环境。 在中心的工作也将加深我们对重要但 迄今为止，人们对科学问题知之甚少， 表观遗传变异的重要性，以及动态和 控制生物系统行为的定量方面。中心 将开发功能性基因组和计算方法， 系统的大规模数据收集，并适用于类似的 研究其他生物，包括人类。该中心将吸引和培训 在基因组研究中，许多研究人员的背景是 物理，数学和其他非生物医学学科，谁将继续 在这个学科的界面上工作。因此，该中心可以作为一个原型 为后续的实验和计算实验室， 来理解基因组的功能。

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.