Mechanisms underlying pattern formation in S. cerevisiae colonies

酿酒酵母菌落模式形成的机制

• 批准号: 7981244
• 负责人: SAUL M HONIGBERG
• 金额: $ 45万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-02 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981244
• 关键词: Biological Assay; Biology; Catheters; Cell Wall; Cells; Collection; Communication; Communities; Development; Disease; Feedback; Gene Expression; Genetic; Goals; Health; Heart Valves; Human; Lead; Mediating; Medical Device; Methods; Microbial Biofilms; Mitogen-Activated Protein Kinases; Molecular Analysis; Nosocomial Infections; Pathogenicity; Pathway interactions; Patients; Pattern; Pattern Formation; Play; Prevention; Production; Research; Role; Saccharomyces cerevisiae; Saccharomycetales; Signal Pathway; Signal Transduction; Yeasts; base; cell type; fungus; intercellular communication; mortality; mutant; public health relevance; research study

DESCRIPTION (provided by applicant): Pattern formation, defined as the creation of a predictable arrangement of cell types in space, is the lynchpin of development within metazoans. Pattern formation also occurs in fungi, but very little is known about the mechanisms underlying fungal pattern formation. Because patterns of cells types form during the development of fungal biofilms, an understanding of the mechanisms of fungal pattern formation could lead to better treatment and prevention of pathogenic biofilms. Currently, these biofilms are a leading cause of mortality from hospital- acquired infections. Our long-term objective is to understand the mechanisms underlying pattern formation within colonies of the budding yeast S. cerevisiae. The proposed research initiated with the discoveries that 1) colonies of S. cerevisiae develop sharply defined layers of sporulated cells interspersed with regions of unsporulated cells, 2) cell-to-cell signaling mediated by the Rim101 pathway and alkaline pH are required for this sporulation pattern. The specific goal of the proposal is to determine how signals and signaling pathways regulate pattern formation in colonies. This goal will be accomplished using mutants defective in the Rim101 pathway or in another pathway implicated in colony sporulation (Cell Wall Integrity pathway), and by identifying other mutants defective in colony sporulation. The role of these pathways in sporulation patterns will be determined using genetic assays for cell-to-cell signaling, molecular analysis of pathway activation, and cytological methods for visualizing patterns of sporulation and gene expression within colony sections. PUBLIC HEALTH RELEVANCE: When fungi grow as biofilms on medical devices such as catheters and heart valves, they can be deadly to patients. Central to the pathogenicity of biofilms is the organization of different cell types within this fungal community. In this proposal, colonies of the yeast S. cerevisiae will be used to investigate how communication between cells can lead to organized patterns of cell types within fungal communities.

描述（由申请人提供）：模式形成，被定义为在空间中可预测的细胞类型的可预测布置，是后生动物内发育的林奇宾。真菌也发生了模式形成，但对真菌模式形成的机制知之甚少。由于在真菌生物膜开发过程中形成细胞类型的模式，因此对真菌模式形成机制的理解可能会导致更好的治疗和预防致病性生物膜。目前，这些生物膜是医院感染死亡的主要原因。 我们的长期目标是了解萌芽的酿酒酵母菌落内的基本模式形成的机制。提出的研究提出的研究是：1）酿酒酵母的菌落形成了与未孢子细胞区域散布的孢子细胞的明确定义的层，2）这种孢子形态需要由RIM101途径和碱性pH介导的细胞到细胞信号传导。该提案的具体目标是确定信号和信号通路如何调节菌落中的模式形成。该目标将使用RIM101途径中有缺陷的突变体或涉及菌落孢子形成（细胞壁完整性途径）的另一个途径中的突变体来实现，并通过鉴定其他在菌落孢子形成中有缺陷的突变体。这些途径在孢子形成模式中的作用将使用用于细胞到细胞信号传导的遗传测定，途径激活的分子分析以及可视化菌落切片内孢子形成和基因表达模式的细胞学方法。 公共卫生相关性：当真菌在医疗设备（例如导管和心脏瓣膜）上生物膜生长时，它们可能对患者致命。生物膜致病性的核心是该真菌群落中不同细胞类型的组织。在此提案中，酿酒酵母的菌落将用于研究细胞之间的通信如何导致真菌群落内细胞类型的有组织模式。