Mechanisms underlying pattern formation in S. cerevisiae colonies

描述（由申请人提供）：模式形成，定义为在空间中创建可预测的细胞类型排列，是后生动物发育的关键。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在真菌生物膜的发育过程中形成，因此了解真菌模式形成的机制可以更好地治疗和预防致病性生物膜。目前，这些生物膜是医院获得性感染导致死亡的主要原因。我们的长期目标是了解在萌芽酵母酿酒酵母菌落内形成模式的机制。本研究发现：1)酿酒酵母菌落发育出清晰的有孢子细胞层，其间穿插着无孢子细胞区域；2)这种产孢模式需要由Rim101通路介导的细胞间信号传导和碱性pH。该提案的具体目标是确定信号和信号通路如何调节殖民地的模式形成。这一目标将通过在Rim101途径或与菌落孢子形成有关的另一途径（细胞壁完整性途径）中存在缺陷的突变体，以及通过鉴定其他在菌落孢子形成中存在缺陷的突变体来实现。这些途径在产孢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和细胞学方法来确定，这些方法用于可视化产孢模式和菌落切片内的基因表达。

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.