PROJECT 7

项目7：细菌细胞的调节和整合(LAUB)(#34-37) 我们阐明了细菌细胞中调节模块的设计原则，重点是信号 处理信息的转导系统。组氨酸激酶在调节细菌中起着重要作用。 生理学。我们开发并使用了系统级工具来映射激酶和 新月桂枝杆菌的底物。我们的研究发现，组氨酸激酶表现出很大的动力学偏好 其体内同源底物的体外研究导致了快速定位信号转导的新技术 细菌中的途径。这使得我们能够证明，Caulbacter细胞周期是由一种整合的 一种基因回路，利用受调节的转录、蛋白分解和磷酸化来产生细胞内的振荡 主细胞周期调节因子CtrA15的活性。我们还确定了第一个真正的细胞周期检查点 证明了真核生物的这一关键调控原理也被用于原核生物。 最后，我们使用计算来预测哪些残基解释了激酶底物的专一性。 相互作用，并造成突变，将一种蛋白激酶(EnvZ)的特异性转换为几种 其他。私家侦探迈克尔·劳布曾是鲍尔研究员，现在是麻省理工学院生物学助理教授。 新项目7：植物发育模块的生活史限制(奎奇)(#38) 我们询问了遗传变异、母体效应和伴侣水平如何决定发育轨迹。 和拟南芥的适合度。植物不能移动，必须适应它们所经历的条件。 适应取决于他们的遗传构成、母亲传递的非孟德尔效应，以及 监护人级别。我们调查了控制生活史的三个性状的变异来源(开花时间， 种子产量等)：由于环境压力、母体效应和等位基因而暴露出来的隐蔽的遗传变异 不同地理群体之间的差异。我们之前曾展示过，更改HspQO级别会揭示 神秘的遗传变异，现在已经绘制了这些特征的基因座图，并发现其中一个特征识别出一种糖依赖 循环系统。我们发现，环境植物体验的不同会产生深远的影响 这些差异是通过胚珠传播的，而不是通过花粉。这些 母体效应依赖于光敏色素对光的感知，并与光敏色素的效应显示出复杂的相互作用 降低Hsp90水平。最后，我们检查了不同地理分离株之间的差异；他们显示 很大的变异，并且大部分变异响应(或增加或减少)Hsp90降低 活动24.这项工作揭示了生态上重要的发育性状的复杂调节和 采取综合办法理解它们的重要性。克里斯汀·奎奇，项目负责人， 曾是鲍尔研究员，2006年加入模块生物学中心，现在是基因组学助理教授 华盛顿大学理科专业。

Project 7: Regulation and integration in bacterial cells (Laub) (#34-37) We elucidated the design principles of regulatory modules in bacterial cells, with a focus on the signal transduction systems that process information. Histidine kinases play a major role in regulating bacterial physiology. We developed and used system-level tools to map the connections between kinases and substrates in Caulobacter crescentus¿. Our finding that histidine kinases exhibit a large kinetic preference in vitro for their in vivo cognate substrates led to new techniques for rapidly mapping signal transduction pathways in bacteria. These allowed us to show that the Caulobacter cell cycle is driven by an integrated genetic circuit that uses regulated transcription, proteolysis, and phosphorylation to produce oscillations in activity of the master cell cycle regulator CtrA15. We also identified the first bona fide cell cycle checkpoint in Caulobacter, demonstrating that this key principle of regulation in eukaryotes is also used in prokaryotes. Finally, we used computation to predict which residues account for the specificity of kinase-substrate interactions, and made mutations that switched the specificity of one protein kinase (EnvZ) to that of several others. Michael Laub, the PI, was a Bauer Fellow and is now Assistant Professor of Biology at MIT. New project 7: Life-history constraints on developmental modules in plants (Queitsch) (#38) We asked how genetic variation, maternal effects and chaperone levels determine developmental trajectories and fitness of Arabidopsis thaliana. Plants are not motile and must adapt to the conditions they experience. Adaptation depends on their genetic constitution, non-Mendelian effects transmitted from their mothers, and chaperone levels. We have investigated three sources of variation in traits that control life history (flowering time, seed yield, etc.): cryptic genetic variation that is exposed by environmental stress, maternal effects, and allelic differences between different geographic populations. We previously showed that altering HspQO levels reveals cryptic genetic variation, have now mapped the loci for these traits and find that one of them identifies a sugardependent cyclin. We discovered that differences in the environment plants experience have profound effects on their progeny and that these differences are transmitted through the ovule but not through pollen. These maternal effects depend on light sensing by phytochromes and show complex interactions with the effects of reducing Hsp90 levels. Finally, we examined the variation between different geographic isolates; they show substantial variation, and much of the variation responds (either increasing or decreasing) to reducing Hsp90 activity24. This work has revealed the complex regulation of ecologically important developmental traits and the importance of taking an integrated approach to understanding them. Christine Queitsch, the project leader, was a Bauer Fellow, joined the Center for Modular Biology in 2006 and is now Assistant Professor of Genome Sciences at U Washington.