PROJECT 7

项目7

• 批准号: 7695418
• 负责人: MICHAEL B ELOWITZ
• 金额: $ 7.5万
• 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/7695418
• 关键词: Accounting; Bacteria; Bacterial Physiology; Biology; Caulobacter; Cell Cycle; Cell Cycle Checkpoint; Cells; Complex; Computer information processing; Condition; Constitution; Cyclins; Development; Environment; Eukaryota; Eukaryotic Cell; Exhibits; Flowers; Genetic; Genetic Transcription; Genetic Variation; Genome; In Vitro; Kinetics; Light; Maps; Molecular Chaperones; Mothers; Mouse-ear Cress; Mutation; Phosphorylation; Phosphotransferases; Phytochrome; Plants; Play; Pollen; Prokaryotic Cells; Protein Kinase; Proteolysis; Regulation; Role; Science; Seeds; Signal Transduction; Signal Transduction Pathway; Source; Specificity; Substrate Interaction; System; Techniques; Time; Variant; Washington; Work; design; experience; fitness; geographic population; in vivo; life history; maternal stress; preference; professor; protein-histidine kinase; tool; trait

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.

项目7：细菌细胞中的调控和整合（Laub）（#34-37） 我们阐述了细菌细胞中调节模块的设计原则，重点是信号 处理信息的传导系统。组氨酸激酶在调节细菌内毒素的作用中起主要作用。 physiology.我们开发并使用了系统级工具来绘制激酶和 新月柄杆菌中的底物。我们的发现是组氨酸激酶表现出很大的动力学偏好， 在体外的同源底物导致了新的技术，快速映射信号转导 细菌的路径。这些使我们能够表明，柄杆菌细胞周期是由一个整合的 一种基因回路，利用调节的转录、蛋白水解和磷酸化来产生振荡， 主细胞周期调节因子CtrA 15的活性。我们还确定了第一个真正的细胞周期检查点， 柄杆菌，表明真核生物中的这一关键调节原则也用于原核生物。 最后，我们利用计算来预测哪些残基解释激酶-底物的特异性 相互作用，并进行突变，将一种蛋白激酶（EnvZ）的特异性转换为几种蛋白激酶的特异性。 他人迈克尔·劳布，PI，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（Queitsch）（#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 和适合度的关系。植物没有运动能力，必须适应它们所经历的条件。 适应性取决于他们的遗传结构，从母亲那里遗传来的非孟德尔效应， 伴侣水平。我们已经调查了控制生活史的性状变异的三个来源（开花时间， 种子产量等）：环境压力、母体效应和等位基因暴露的神秘遗传变异 不同地理群体之间的差异。我们先前表明，改变HspQO水平揭示了 神秘的遗传变异，现在已经绘制了这些特征的基因座，并发现其中一个识别了糖依赖性 细胞周期蛋白。我们发现植物所经历的环境差异会产生深远的影响 这些差异是通过胚珠而不是通过花粉传递的。这些 母体效应依赖于光敏色素的光感，并与 降低HSP 90水平。最后，我们研究了不同地理分离株之间的变异;它们显示， 实质性的变化，并且大部分变化响应于（增加或减少）减少Hsp 90 活动24.这项工作揭示了生态上重要的发育特征的复杂调节， 采取综合办法理解这些问题的重要性。项目负责人克莉丝汀奎奇， 我是鲍尔研究员，2006年加入模块生物学中心，现在是基因组助理教授 华盛顿大学的科学系。