Mechanisms underlying cell-fate patterns in yeast communities

酵母群落细胞命运模式的潜在机制

基本信息

批准号：
8626605
负责人：
SAUL M HONIGBERG
金额：
$ 40.77万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-02 至 2017-05-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8626605
关键词：
Address Adopted Agar Alkalies Apoptosis Apoptotic Autophagocytosis Band Cell Biological Assay Blood Catheters Cell Death Cell Differentiation process Cell Wall Cell physiology Cells Cessation of life Communication Communities Development Gene Expression Profile Genetic Epistasis Genotype Goals Health Heart Valves Hospitals Immune Implant Individual Infection Lead Location Medical Device Microbe Microbial Biofilms Molecular Monitor Mycoses Necrosis Nosocomial Infections Nutrient Organism Pathogenicity Pathway interactions Pattern Pattern Formation Phenotype Phosphorylation Play Propidium Diiodide Proteins Proteolysis Public Health Relative (related person)Research Role Signal Pathway Signal Transduction Stress Surface Testing Time Yeasts cell type effective therapy human disease interest novel strategies prevent programs research study response self organization transcription factor tumor

项目摘要

DESCRIPTION (provided by applicant): As nutrients become limiting in developing yeast colonies, at least 3 different cell differentiation programs can be induced: 1) pseudohyphal differentiation (a foraging response), 2) sporulation, and 3) programmed cell death. Intriguingly, a key aspect determining an individual cell's choice of fate within a colony is geographical; different regions of the colony adopt different fates. Indeed, we recently discovered that sharp boundaries form between layers of sporulated and unsporulated cells in colonies. Pattern formation within yeast communities likely provides functional advantages over unpatterns communities. The long-range goal of the Honigberg lab is to identify the mechanisms that regulate the self- organization of yeast colonies from homogeneous to highly patterned communities. Given the sharp boundaries between the colonies regions mentioned above, a key part of these mechanisms is likely cell-to- cell signaling. The central hypothesis of the current proposal is that a layer of cells in colonies near the agar surface undergoes apoptotic programmed cell death (PCD), providing nutrients or other signals the stimulate sporulation in an overlying layer of cells. Three complementary approaches are taken to address the above hypothesis. The first approach is to determine the activity of signaling pathways and cellular processes as colonies develop. Specifically, we will suspend colonies and assay the suspended cells using molecular approaches such as protein phosphorylation assays or and cytological approaches such as monitoring apoptotic markers. The second approach is to section colonies to investigate spatial patterns of gene expression, protein localization and cell differentiation. The last approach is to monitor cell fates in communities containing mixtures of strains of different genotypes to test hypotheses regarding the cell autonomy required for PCD, sporulation and patterning in colonies. One of the most ancient and fundamental purposes for communication between organisms may have been to allow these microbes to self-organize into functional communities. Yeast colonies provide an opportunity to investigate this type of communication. In addition to the scientific interest, the health relevance of the proposed research derives from the fact that organized communities of pathogenic yeast termed biofilms can form on implanted medical devices, and that the organization of these biofilms contributes significantly to the lethality of hospital-acquired fungal infections.

描述（由申请人提供）：随着养分受到发展酵母菌菌落的限制，至少可以诱导3种不同的细胞分化程序：1）假氢分化（a觅食反应），2）孢子形成和3）孢子虫。有趣的是，确定单个细胞在殖民地内选择命运的关键方面是地理的。殖民地的不同地区采用不同的命运。确实，我们最近发现菌落中孢子细胞和未孢子细胞的层之间形成了尖锐的边界。酵母社区内的模式形成可能比不公平社区具有功能优势。 Honigberg实验室的远程目标是确定调节从同质到高度图案的酵母菌菌落自我组织的机制。鉴于上述菌落区域之间的尖锐边界，这些机制的关键部分可能是细胞对细胞信号传导。当前建议的中心假设是，琼脂表面附近菌落中的一层细胞经历了凋亡的程序性细胞死亡（PCD），从而提供营养或其他信号，刺激细胞上层层中的孢子形成。采用三种补充方法来解决上述假设。第一种方法是随着菌落的发展，确定信号通路和细胞过程的活性。具体而言，我们将使用诸如蛋白质磷酸化测定或细胞学方法（例如监测凋亡标记物）等分子方法进行悬浮并测定悬浮的细胞。第二种方法是研究基因表达，蛋白质定位和细胞分化的空间模式。最后的方法是监测包含不同基因型菌株混合物的群落中的细胞命运，以测试有关菌落中PCD所需的细胞自治，孢子形成和构图的假设。生物体之间交流的最古老，最基本的目的之一可能是使这些微生物自组织成功能社区。酵母菌殖民地提供了调查这种交流的机会。除了科学兴趣外，提议的研究的健康相关性源于以下事实：植入的医疗设备的有组织的致病酵母社区可以形成生物膜，并且这些生物膜的组织对医院获得的真菌感染的致命性有很大贡献。