Genetic Analysis of Phase Variation in Myxococcus

表型异质性（又称表型或阶段变异）发生时，一个群体中的一个生物子集调节可逆开关，使他们能够表达不同的细胞成分集。黄粘球菌（Myxococcus xanthus）是一种生活在土壤中、生产抗生素的细菌，其戏剧性的社会活动，包括群体扩张和发展，已经产生了大量关于细胞-细胞相互作用、信号传导和多细胞合作行为的信息。这些社会过程与M. xanthus细胞经历阶段变化的能力密切相关，这产生了两种相互转换的细胞类型，称为黄色和褐色，它们在群体，生存和发育方面的能力差异很大。野生型菌落表现出表型异质性，因为它们包含黄色，蜂群和棕色，非蜂群变体的混合物。值得注意的是，黄色和棕色变异对种群的长期生存都至关重要，这表明黄原霉的表型异质性进化出了一种故障安全机制，以确保维持细胞类型的生存。本研究的目的是利用分子、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色转换的机制，并以了解两种细胞类型之间的生物学相互作用为长期目标。为了实现这一目标，将对表达依赖于相的基因的功能进行表征，并确定相变异的调控因子，包括主调控因子。由于表型变异影响黄粘球菌生命周期的多个方面，这些实验的结果可能会导致一个连贯的模型，显示黄粘球菌如何协调其社会发育途径。此外，利用代表性土壤生物黄原菌获得的结果可能更全面地描绘出表型变异在环境生物适应度中的作用。广泛影响：黏液球菌是研究微生物发育和分化的理想微生物。该项目将支持几名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的培训，还将获得使用生物信息学和计算工具的培训，这将是解决相位变化复杂性所必需的。随着有关相位变化的具体问题的答案的揭示，一种潜在的新型信号系统的更大图景有望出现，这可能与自然界中的微生物群落广泛相关。

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.