Genetic Analysis of Phase Variation in Myxococcus

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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.