DISSECTING & EVOLVING MATING MODULE OF BUDDING YEAST

解剖

• 批准号: 7557325
• 负责人: Andrew Murray
• 金额: $ 31.98万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7557325
• 关键词: Affect; Biological; Biological Process; Cell Cycle Arrest; Cells; Classification; Collection; Communication; Conflict (Psychology); DNA Damage; Discrimination; Evolution; Exposure to; Face; Feedback; Future; Gene Deletion; Gene Expression; Genes; Genetic; Genome; Individual; Logic; Maps; Molecular; Monitor; Mutation; Nature; Numbers; Output; Partner in relationship; Pathway interactions; Performance; Personal Satisfaction; Phenotype; Pheromone; Physiological; Population; Process; Proliferating; Protein Kinase; Range; Reproducibility; Research; Role; Saccharomycetales; Shapes; Signal Pathway; Signal Transduction; Specificity; Structure; Techniques; Theoretical Studies; Variant; Work; Yeasts; behavior test; cell behavior; design; expectation; gene induction; insight; novel; pressure; research study; response; small molecule; theories

A functional module is a collection of molecules that interact with each other to accomplish a biological function. This group will study the structure, function, and evolution of the mating module from budding yeast, combining experiment and theory to reap the full benefit of these complementary approaches. The proposed work has four aims: 1) To use systematic genetic approaches to identify, characterize, and analyze new genes involved in mating. 2) To monitor and dissect the function and mechanism of the mating module. Theoretical analysis suggested and experiment has confirmed that individual yeast cells shows a switch-like response to pheromone treatment. The group will investigate this response and use a variety of techniques to figure out how cells detect very shallow concentration gradients over a wide range of pheromone concentrations. 3) To investigate the robustness of mating. The group will ask how quantitative variation in one or more parameters of the mating module affect its performance, by controlled perturbation of the four protein kinases in the module. They will monitor multiple aspects of mating, including mating efficiency, mating discrimination, chemotropism, cell cycle arrest and, gene induction to ask if mating is more robust to perturbation than the various processes (arrest, gene expression, chemotropism) that induce it. 4)To evolve the mating module in three directions: a) Speciation (altered specificity) to create novel budding yeast populations that mate within themselves but not to the lab strains they were derived from. b) Altered function (altered logic). At present, pheromone signaling is rapidly reversible, but it will be evolved so that transient exposure to pheromone leads to prolonged activation of the pathway. c) Cross-communication (altered inter module connectivity). Cells will be evolved so that the input of one pathway becomes connected to the output of another.

功能模块是相互相互作用以完成生物学功能的分子集合。该小组将研究来自萌芽酵母的交配模块的结构，功能和演变，结合实验和理论，从而获得这些互补方法的全部好处。拟议的工作有四个目标： 1）使用系统的遗传方法来识别，表征和分析涉及交配的新基因。 2）监视和剖析交配模块的功能和机制。理论分析表明，实验证实了各个酵母细胞对信息素治疗的开关样反应。该小组将研究这一响应，并使用多种技术来找出细胞如何在各种信息素浓度范围内检测到非常浅的浓度梯度。 3）研究交配的鲁棒性。该组将通过控制模块中的四种蛋白激酶的扰动来询问交配模块一个或多个参数中的定量变化如何影响其性能。他们将监视交配的多个方面，包括交配效率，交配歧视，趋化性，细胞周期停滞和基因诱导，以询问交配是否比诱导它的各种过程（停滞，基因表达，趋化性）更强大。 4）在三个方向上演变配合模块： a）形成（改变特异性）以创建新颖的芽酵母菌种群，这些酵母菌种群在自己体内，而不是与他们得出的实验室菌株相配。 b）功能变化（逻辑更改）。目前，信息素信号传导迅速可逆，但会进化，以便瞬时暴露于信息素导致途径的延长激活。 c）交叉通信（更改模块间连接）。细胞将进化，以使一个途径的输入与另一个途径的输出连接。