Mechanisms Driving Emergent Behaviors during Myxococcus xanthus Development

生物体如何构建大小和形状可控的结构，以及细胞如何选择不同的命运，是生物学中的基本问题。粘球菌xanthus提供了一个独特的机会来回答这些问题：当饥饿时，这些杆状细菌在溪流中移动，并建立土丘，产生称为子实体的结构，同时一些细胞分化成圆形孢子。其他细胞死亡或留在子实体外面作为杆。细胞之间的短程信号（称为C-信号）协调孢子分化的流和丘形成，但这是如何发生的还不完全清楚。为了了解这一过程，研究人员将确定哪些基因参与其中，它们的表达在流动和丘形成过程中如何变化，哪些基因引发细胞形状的变化，以及细胞如何交流。细胞间的相互作用影响着所有生物的生命。进一步了解细胞间的相互作用如何驱动行为，将使社会受益，例如，提供信息，允许操纵微生物群落用于污染和气候控制，并增加生物能源和粮食生产的潜力。该项目还将通过为学生提供强有力的跨学科培训以及通过互动演示和外联活动提高公众科学素养和参与度来造福社会。粘球菌是一个有吸引力的模型系统，因为多细胞发育在实验室条件下快速同步发生。M. xanthus在复杂性上可与低等真核生物相媲美，并包括真核生物的特征，例如使用短距离信号来协调紧急行为。通过研究M. xanthus利用短程信号来协调流和丘形成与孢子分化，该项目将提供深入了解在发展中常见的紧急性质，如多细胞结构的组装和细胞命运的决定，使用一个高度遗传易处理的系统。获得的知识和开发的方法也将促进对微生物群落（微生物组）的研究。多物种微生物组及其环境的复杂性使得发现其潜在机制并了解它们如何有助于新兴特性具有挑战性。特别是，短距离信号的作用尚未得到充分研究。该研究小组的重点是如何M。Xanthus使用短程信号来驱动连续的涌现行为，这将推进有可能改变对微生物组特性如何出现的思考的知识。他们将使用广泛的方法，包括显微镜，遗传学，生物化学和数学建模。该团队在研究细菌中的信号传导和基因调控、从显微图像中提取数据以及使用数据驱动的计算模拟来解释结果并指导进一步的实验方面拥有丰富的经验。最近，他们设计了一种方法来可视化M。xanthus发育新的方法为这项工作铺平了道路，这项工作也依赖于创新的策略来识别驱动紧急行为的基因。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

How organisms build structures of controlled size and shape, and with cells that adopt alternative fates, are fundamental questions in biology. Myxococcus xanthus provides a unique opportunity to answer these questions: when starved, these rod-shaped bacteria move in streams and build mounds that produce structures, called fruiting bodies, while at the same time some cells differentiate into round spores. Other cells die or remain outside of the fruiting bodies as rods. Short-range signaling (called C-signaling) between cells coordinates streaming and mound formation with spore differentiation, but how this occurs is not fully known. To understand the process, the research will identify which genes are involved, how their expression changes during streaming and mound formation, what genes initiate change in cell shape, and how the cells communicate. Cell-cell interactions impact the life of all organisms. Further understanding of how cell-cell interactions drive behaviors will benefit society by, for example, providing information that will permit manipulation of microbial communities for pollution and climate control, and increase the potential for bioenergy and food production. The project will also benefit society by providing strong interdisciplinary training to students and by increasing public scientific literacy and engagement through interactive presentations and outreach events.Myxococcus xanthus is an attractive model system because multicellular development occurs rapidly and synchronously under laboratory conditions. The signaling and sensory capabilities of M. xanthus rival those of lower eukaryotes in complexity and include eukaryotic-like features, such as the use of short-range signaling to coordinate emergent behaviors. By focusing on how M. xanthus uses short-range signaling to coordinate streaming and mound formation with spore differentiation, the project will provide deep insight into emergent properties found commonly in development, such as assembly of multicellular structures and cell fate determination, using a highly genetically tractable system. The knowledge gained and methods developed will also catalyze research on microbial communities (microbiomes). The complexity of multispecies microbiomes and their environments makes it challenging to discover the underlying mechanisms and understand how they contribute to emergent properties. In particular, the role of short-range signaling is understudied. The research team's focus on how M. xanthus uses short-range signaling to drive successive emergent behaviors will advance knowledge that has potential to transform thinking about how the properties of microbiomes emerge. They will use a broad range of approaches including microscopy, genetics, biochemistry, and mathematical modeling. The team has extensive experience investigating signaling and gene regulation in bacteria, extracting data from microscopic images, and using data-driven computational simulations to interpret results and guide further experiments. Recently, they devised methods to visualize the shape and gene expression of individual cells during M. xanthus development. The new methodology paves the way for the work, which also relies on innovative strategies to identify genes driving emergent behaviors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.