PROJECT 2

项目2

• 批准号: 7695397
• 负责人: DAVID R NELSON
• 金额: $ 8.51万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7695397
• 关键词: Behavior; Binding; Biological Process; Biology; Cell surface; Cells; Chromosomes; Collaborations; Discrimination; Dynein ATPase; Endopeptidases; Environment; Evolution; Gene Expression; Generations; Length; Meiosis; Microtubules; Modeling; Molecular Probes; Motor; Noise; Numbers; Partner in relationship; Peptide Hydrolases; Pheromone; Physics; Play; Population; Promoter Regions; Rate; Role; Saccharomycetales; Slide; Specific qualifier value; Speed; TATA Box; Testing; Theoretical model; Time; Variant; asexual; in vivo; mathematical model; research study; theories

Project 2: Theoretical analysis of functional modules (Fisher, years 1-3; Barkai, years 4-5) (#15-20) We have built and analyzed theoretical models and used them to predict and analyze the behavior of modules in vivo. We believe that mathematical models are needed to reach a full understanding of biological processes and two theorists have played major roles in the Center for Modular Biology. From 2002 to 2006, Daniel Fisher (Physics, now at Stanford) interacted with a number of groups on different problems, including the generation of segment polarity in Drosophila27, the factors that specify the length of the meiotic spindle (collaboration with T. Mitchison), and predicting the speed of evolution (collaboration with A. Murray). Experiments on the distribution and dynamics of microtubules suggest that microtubules are nucleated in a region near the chromosomes, and then transported polewards by a plus-end-directed motor (Eg5) that slides microtubules of opposite polarities past one another28. The model invokes competition between these motors and dynein, a minus-end-directed motor that clusters minus ends. Several predictions of this model have been confirmed by experiments29. We also produced a new theory for the rate of evolution in asexual populations and then performed experiments that confirmed key predictions of the theory and ruled out alternative models, including the extreme form of clonal interference. For the last two years, the PI on this project has been Naama Barkai; who has collaborated on projects examining the mating (project 3, collaboration with A. Murray) and sporulation (new project 6, collaboration with S. Ramanathan) of budding yeast. In mating, theory suggests that cells can decide between two equally attractive partners only if some of the protease that degrades mating pheromones is bound to the cell surface. We have refined this model and verified that successful discrimination requires cell-bound protease. Sporulation shows wide cell-to-cell variation. We have quantified the variable timing through the different steps of sporulation and are using theory and experiment to probe the molecular circuits that control sporulation, and ask how variability might be advantageous in a fluctuating environment. Finally, we have performed experiments to test the hypothesis that the presence of the TATA-box in promoter regions confers both noise and evolvability in gene expression (collaboration with A . Murray).

项目2：功能模块的理论分析（Fisher，1-3年; Barkai，4-5年）（#15-20） 我们已经建立和分析了理论模型，并使用它们来预测和分析模块的行为 in vivo.我们相信，要想全面了解生物过程，需要建立数学模型 还有两位理论家在模块生物学中心发挥了重要作用。从2002年到2006年，丹尼尔费舍尔 （物理学，现在在斯坦福大学）与许多团体就不同的问题进行了互动，包括一代 在果蝇27节极性，指定的因素，减数分裂纺锤体的长度（与合作 T. Mitchison），以及预测进化的速度（与A。Murray）。的实验 微管的分布和动力学表明，微管是在一个区域附近的核 染色体，然后通过一个正末端导向的马达（Eg 5）向极运输，该马达使染色体的微管滑动， 相反的极性彼此经过28.该模型引发了这些马达和动力蛋白之间的竞争， 负端导向的马达聚集负端。该模型的几个预测得到了证实， 实验29.我们还提出了一个关于无性种群进化速度的新理论， 进行了实验，证实了该理论的关键预测，并排除了替代模型，包括 克隆干扰的极端形式。 在过去的两年里，这个项目的PI一直是纳马巴凯;他在项目上进行了合作 研究交配（项目3，与A. Murray）和孢子形成（新项目6，合作 链球菌（Ramanathan）芽殖酵母。在交配中，理论表明细胞可以在两个之间做出平等的决定， 只有当一些降解交配信息素的蛋白酶结合到细胞表面时，才能吸引有吸引力的伴侣。 我们已经完善了这个模型，并验证了成功的歧视需要细胞结合蛋白酶。 孢子形成显示出细胞间的广泛差异。我们已经通过不同的步骤量化了可变时间 并正在使用理论和实验来探索控制孢子形成的分子电路， 询问可变性如何在波动的环境中发挥优势。最后，我们表演了 实验来检验启动子区域中TATA盒的存在赋予噪声和非噪声的假设。 和基因表达的进化性（与A . Murray）。