Mechanisms underlying pattern formation in S. cerevisiae colonies

描述（由申请人提供）：模式形成，定义为细胞类型在空间中的可预测排列，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病原性生物膜。目前，这些生物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芽殖酵母S.啤酒。本研究首先发现：1）S.酿酒酵母形成清晰的孢子形成细胞层，散布有未孢子形成细胞的区域，2）由Rim 101途径介导的细胞间信号传导和碱性pH是这种孢子形成模式所需的。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。这一目标将使用Rim 101途径或涉及菌落孢子形成的另一途径（细胞壁完整性途径）缺陷的突变体，并通过鉴定菌落孢子形成缺陷的其他突变体来实现。这些途径在孢子形成模式中的作用将使用细胞间信号传导的遗传测定、途径激活的分子分析和用于使菌落切片内孢子形成和基因表达模式可视化的细胞学方法来确定。 公共卫生相关性：当真菌作为生物膜生长在导管和心脏瓣膜等医疗器械上时，它们可能对患者致命。生物膜致病性的核心是真菌群落中不同细胞类型的组织。在这个提议中，酵母S.酿酒酵母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.