CAREER: Self-organization mechanisms in Myxococcus xanthus swarms

职业：黄色粘球菌群的自组织机制

• 批准号: 0845919
• 负责人: Oleg Igoshin
• 金额: $ 64万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0845919&HistoricalAwards=false
• 关键词: CAREER; Self; organization; mechanisms; Myxococcus

Intellectual MeritIn recent years the ubiquity of microbial communities in nature has become apparent. For example, bacterial surface-associated communities, biofilms, are the most common mode of bacterial growth and are oftentimes resistant to environmental stress or antimicrobial treatment. However, it is still not clear how individual cells self-organize into these communities and how a community as a whole responds to environmental cues. This project aims to discover the mechanisms of self-organization in dynamic single-species biofilms (swarms). In these swarms, bacteria display collective surface motility, cooperatively sense the environment, execute collective developmental programs, and often differentiate into distinct cell types that perform specialized functions. Research on mechanisms of biofilm formation addresses questions similar to those in developmental biology; connecting macroscopic phenotypes and biochemical pathways in individual cells. Even when the genome composition of the cells is known, relating mutations affecting emergent spatio-temporal patterns to mechanisms of intercellular signaling and motility remains a challenge. Decoding these mechanisms from phenotypic observations is a complex reverse-engineering problem that cannot be solved solely by traditional experimental research. A complementary approach combining agent-based modeling and biostatistical image quantification with experimentation will address this problem. This research focuses on self-organization in spreading or aggregating biofilms formed by Myxococcus xanthus, an important model organism for studying microbial cooperation, development, and collective motility. This bacterium uses two motility systems and multiple sensory and signaling pathways to move over surfaces, forming a variety of population patterns. These patterns reveal motility coordination of individual cells as well as their ability to collectively sense and respond to environmental cues. This project will develop an approach to decode diverse phenotypes and uncover intercellular interactions using mathematical models that mimic experimentally observed patterns.Broader ImpactBroader impacts of the project include the development of new methods that bridge gaps between subcellular, cellular, and multicellular scales in spreading bacterial biofilms. Despite the focus on a specific model system (M. xanthus), the project will elucidate general mechanisms behind collective motility behavior. More than 50 bacterial genera use surface motility to form various types of dynamic biofilms, and many of these are important in industry. The methods and software developed for this project will be made available to the Myxobacteria research community worldwide. Developed tools and results of the research will be incorporated into a M. xanthus model organism database (xanthusBase) based on Wikipedia principles of community participation. Answering complex biological questions in the post-genomic era will require a new generation of life scientists with cross-disciplinary training in combining experimental and computational methods. To broaden the impact of this project, the PI seeks to improve and expand Systems Biology education on various levels, attract a diverse pool of talented students to the field of computational and systems biosciences, and contribute significantly to their training. The cornerstone of the educational component of this project is training for postdoctoral scholars, graduate students, undergraduate students, and high school teachers and their students. In addition the training includes a plan for outreach to include students from members of underrepresented groups.

智力上的优点近年来，微生物群落在自然界中的普遍性已经变得显而易见。例如，细菌表面相关群落、生物膜是细菌生长的最常见模式，并且通常对环境压力或抗微生物处理具有抗性。然而，目前尚不清楚单个细胞如何自我组织成这些社区，以及社区作为一个整体如何对环境线索做出反应。本项目旨在发现动态单物种生物膜（群）中的自组织机制。 在这些群体中，细菌表现出集体的表面运动性，协同感知环境，执行集体的发育程序，并且经常分化成执行专门功能的不同细胞类型。对生物膜形成机制的研究解决了与发育生物学相似的问题;将宏观表型和单个细胞中的生化途径联系起来。即使当细胞的基因组组成是已知的，与突变影响紧急时空模式的细胞间信号传导和运动机制仍然是一个挑战。从表型观察中解码这些机制是一个复杂的逆向工程问题，不能仅仅通过传统的实验研究来解决。一个互补的方法相结合的代理为基础的建模和生物统计图像量化与实验将解决这个问题。本研究的重点是自组织传播或聚集的生物膜形成的粘球菌xanthus，一个重要的模式生物研究微生物的合作，发展，和集体运动。这种细菌使用两种运动系统和多种感觉和信号通路在表面上移动，形成各种种群模式。这些模式揭示了单个细胞的运动协调以及它们集体感知和响应环境线索的能力。该项目将开发一种方法来解码不同的表型，并利用模拟实验观察模式的数学模型来揭示细胞间的相互作用。更广泛的影响该项目的更广泛的影响包括开发新的方法，弥合亚细胞，细胞和多细胞尺度之间的差距，传播细菌生物膜。尽管专注于一个特定的模型系统（M。xanthus），该项目将阐明集体运动行为背后的一般机制。超过50种细菌属利用表面运动性形成各种类型的动态生物膜，其中许多在工业中很重要。为该项目开发的方法和软件将提供给全世界的粘细菌研究界。开发的工具和研究结果将被纳入一个M。xanthus模式生物数据库（xanthusBase）基于维基百科社区参与原则。在后基因组时代解决复杂的生物学问题将需要新一代的生命科学家，他们在结合实验和计算方法方面受过跨学科的训练。为了扩大该项目的影响，PI旨在改善和扩大各级系统生物学教育，吸引各种有才华的学生到计算和系统生物科学领域，并为他们的培训做出重大贡献。 该项目教育部分的基石是培训博士后学者、研究生、本科生和高中教师及其学生。 此外，培训还包括一项外联计划，以包括来自代表性不足群体的学生。