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） 我们已经构建和分析了理论模型，并用它们来预测和分析模块的行为 体内。我们认为需要数学模型以完全了解生物学过程 两位理论家在模块化生物学中心扮演了重要角色。从2002年到2006年，丹尼尔·费舍尔（Daniel Fisher） （物理学，现在在斯坦福 果蝇27中的段极性，指定减数分裂纺锤长度的因素（与 T. Mitchison），并预测进化的速度（与A. Murray的合作）。实验 微管的分布和动力学表明，微管是在附近的区域中成核的 染色体，然后通过末端指导的电动机（EG5）向极点运输，该电动机滑动微管 相反的极性超过了一个又一个28。该模型调用了这些电动机与动力蛋白之间的竞争 减去端定向的电动机，簇减去末端。该模型的几个预测已通过 实验29。我们还为无性群体的进化速率提出了一种新理论，然后 进行了确认该理论的关键预测的实验，并排除了替代模型，包括 克隆干扰的极端形式。 在过去的两年中，该项目的PI一直是Naama Barkai。谁在项目上合作 检查交配（项目3，与A. Murray的合作）和散发（新项目6，合作 与S. ramanathan）的萌芽酵母。在交配中，理论表明细胞可以在两个之间做出同样的决定 只有在某些降解交配信息素的蛋白酶与细胞表面结合时，有吸引力的伴侣。 我们已经完善了该模型，并验证了成功的歧视需要细胞结合的蛋白酶。 孢子形成广泛的细胞对细胞变化。我们已经通过不同的步骤量化了变量时机 孢子形成，并正在使用理论和实验来探测控制孢子形成的分子电路，并且 询问在波动环境中的可变性如何有利。最后，我们表演了 测试启动子区域中Tata-box的存在的假设的实验赋予了两个噪声 以及基因表达中的发展性（与穆雷合作）。