Genetic Analysis of Phase Variation in Myxococcus

粘球菌相变的遗传分析

• 批准号: 1052525
• 负责人: Patricia Hartzell
• 金额: $ 35万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1052525&HistoricalAwards=false
• 关键词: Genetic; Analysis; Phase; Variation; Myxococcus

Phenotypic heterogeneity (aka phenotypic or phase variation) occurs when a subset of organisms in a population regulate a reversible switch that allows them to express alternate sets of cellular components. Myxococcus xanthus is a soil-dwelling, antibiotic-producing, bacterium whose dramatic social activities, including swarm expansion and development, have yielded a wealth of information about cell-cell interactions, signaling and multicellular cooperative behavior. These social processes are linked intimately with the ability of M. xanthus cells to undergo phase variation, which produces two inter-convertible cell types, called yellow and tan, that differ greatly in their abilities to swarm, survive, and develop. Wild-type colonies exhibit phenotypic heterogeneity because they contain a mixture of yellow, swarming and tan, non-swarming variants. Remarkably, both yellow and tan variants are critical for long-term survival of the population, which demonstrates that phenotypic heterogeneity in M. xanthus evolved a fail-safe mechanism to ensure the maintenance cell type survival. This research is aimed at using molecular, genetic, and bioinformatic and computational tools to elucidate the mechanism that allows M. xanthus cells to undergo this remarkable yellow to tan switch with the long-range goal of understanding the biological interplay between the two cell types. Toward this goal, the function of genes whose expression is phase dependent will be characterized and the regulators of phase variation, including the master regulator, will be identified. Because phenotypic variation affects multiple aspects of the M. xanthus lifecycle, the results of these experiments may lead to a coherent model showing how Myxococcus xanthus coordinates its social developmental pathways. Furthermore, results obtained using M. xanthus, a representative soil organism, may paint a more comprehensive picture of the role that phenotypic variation plays in fitness of environmental organisms.Broader Impacts: Myxococcus is an ideal organism to study microbial development and differentiation. This project will support the research of several undergraduate and graduate students who will gain training not only in classical genetics and molecular biology, but also in the use of bioinformatic and computational tools, which will be necessary to address the complexity of phase variation. As answers to specific questions regarding phase variation are revealed, a bigger picture of a potentially novel signaling system is expected to emerge that may be broadly relevant to microbial communities in nature.

表型异质性（又称表型或相位变异）发生在种群中的一个生物体子集调节可逆开关，使它们能够表达交替的细胞组分。黄色粘球菌是一种生活在土壤中的细菌，其引人注目的社会活动，包括群体扩张和发展，已经产生了大量关于细胞间相互作用，信号传导和多细胞合作行为的信息。这些社会过程与M的能力密切相关。xanthus细胞经历相位变化，产生两种相互转换的细胞类型，称为黄色和褐色，它们在群集，生存和发育的能力方面有很大差异。野生型菌落表现出表型异质性，因为它们含有黄色群集和棕褐色非群集变体的混合物。值得注意的是，黄色和棕褐色变体对于种群的长期存活都是至关重要的，这表明M. Xanthus进化出一种故障安全机制，以确保维持细胞类型的存活。本研究旨在利用分子、遗传、生物信息学和计算工具来阐明M。xanthus细胞经历这种显着的黄色到棕褐色的转换，其长期目标是了解两种细胞类型之间的生物相互作用。为了实现这一目标，其表达是相位依赖性的基因的功能将被表征，并且相位变化的调节器，包括主调节器，将被鉴定。由于表型变异影响了M.这些实验的结果可能会导致一个连贯的模型，显示粘球菌xanthus如何协调其社会发展途径。此外，使用M.粘球菌是研究微生物发育和分化的理想微生物。该项目将支持一些本科生和研究生的研究，他们不仅将获得经典遗传学和分子生物学方面的培训，而且还将获得生物信息学和计算工具的使用方面的培训，这对于解决相位变化的复杂性是必要的。 随着有关相位变化的具体问题的答案被揭示，一个潜在的新信号系统的更大的图片预计将出现，可能与自然界中的微生物群落广泛相关。