PROJECT 2

项目2：功能模块的理论分析(Fisher，1-3岁；Barkai，4-5岁)(#15-20) 我们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 在活体内。我们认为，需要数学模型来充分理解生物过程。 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)与许多小组就不同的问题进行互动，包括这一代人 关于果蝇节段的极性，决定减数分裂纺锤体长度的因素(与 和预测进化的速度(与A.Murray合作)。在此基础上进行的实验 微管的分布和动力学表明，微管在附近的区域成核 染色体，然后由一个正端定向马达(EG5)向极地运输，它滑动微管 相反的极性一个接一个地过去28。该模型引发了这些马达和动力蛋白之间的竞争， 负端导向的电机，它聚集在负端。这个模型的几个预测已经被证实 实验29.我们还提出了无性种群进化速度的新理论，然后 进行的实验证实了该理论的关键预测，并排除了其他模型，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Naama Barkai；他在项目上进行了合作 检查交配(项目3，与A·默里合作)和产孢子(新项目6，合作 与S.Ramanathan)发芽酵母。在交配过程中，理论表明细胞可以在两者之间做出平等的选择 只有当一些降解交配信息素的蛋白酶与细胞表面结合时，才能吸引伴侣。 我们改进了这个模型，并验证了成功的区分需要细胞结合的蛋白酶。 产孢量表现出广泛的细胞间变异。我们已经通过不同的步骤量化了可变定时 并正在利用理论和实验来探索控制孢子形成的分子电路，以及 问一问在一个波动的环境中，可变性可能会有什么好处。最后，我们表演了 对启动子区域中TATA盒的存在给出两种噪声的假设进行验证的实验 和基因表达的进化性(与A.默里)。

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).