Mechanisms underlying pattern formation in S. cerevisiae colonies

描述(申请人提供)：图案形成，定义为在空间中创造可预测的细胞类型排列，是后生动物发展的关键。模式形成也发生在真菌中，但对真菌模式形成的机制知之甚少。由于细胞类型的模式是在真菌生物膜的发展过程中形成的，因此了解真菌模式形成的机制可以更好地治疗和预防病原性生物膜。目前，这些生物被膜是医院获得性感染死亡的主要原因。我们的长期目标是了解萌芽酵母菌落内模式形成的潜在机制。这项拟议的研究始于以下发现：1)酿酒酵母菌落形成清晰的孢子化细胞层，其间散布着未形成孢子的细胞区域；2)这种孢子形成模式需要Rim101途径介导的细胞间信号和碱性pH。该提案的具体目标是确定信号和信号通路如何调节群体中的模式形成。这一目标将通过使用在Rim101途径或与菌落孢子形成有关的另一条途径(细胞壁完整性途径)中有缺陷的突变株来实现，并通过鉴定其他在菌落孢子形成中有缺陷的突变体来实现。这些途径在孢子形成模式中的作用将通过细胞间信号的遗传分析、途径激活的分子分析以及菌落切片中观察孢子形成模式和基因表达的细胞学方法来确定。 与公共卫生相关：当真菌作为生物膜在导管和心脏瓣膜等医疗设备上生长时，它们可能会对患者造成致命影响。生物膜致病性的核心是这个真菌群落中不同类型的细胞的组织。在这项提案中，酿酒酵母的菌落将被用来研究细胞之间的交流如何导致真菌群落内细胞类型的有组织模式。

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.