Maintenance and evolution of cooperation in synthetic microbial ecosystems

微生物种群中合作性状的出现（如公共产品的生产）以及它们在搭便车者存在的情况下的维持是进化生物学的中心问题。在第一个资助期，我们的重点是人口噪声对非选择性和选择性条件下合作细菌种群的生长动力学和组成的影响，结合实验和理论。我们发现，在非选择性条件下，不断增长的人口从来没有固定到一个性状，但调整到一个随机的稳态组成。在选择性条件下，我们通过实验验证了我们的理论预测，即人口噪声导致公共产品生产者在群体中的比例短暂增加。为此，我们建立了一个合成的生态系统，并确定了实验条件的合作行为在假单胞菌种群。此外，我们表明，绿脓菌荧光素合成基因的表达是表型异质性的假单胞菌种群，并调制铁的可用性。在未来的资助期内，我们打算扩阔研究范围，并循沿着两条主要研究方向进行。(1)首先，我们将对绿脓菌荧光素生产和消费的基因调控机制及其对生产和非生产菌株生长速率的影响进行更机械的分子理解。以前的理论模型部分忽略了积累的绿脓菌荧光素和生长阶段对铁载体生产的影响。我们将扩展这些模型来解释这一特征，并定量分析外部绿脓菌荧光素对生产菌株和非生产菌株生长动力学的影响。此外，我们计划解开恶臭假单胞菌中绿脓菌荧光素产生和调控的分子机制。具体来说，我们将分析假定的个体调节回路，并将其活动与各种铁可用性条件下的代谢状态和绿脓荧光素产生联系起来。这些分析将提供有关不同环境中细胞行为的调控网络和信息的全面图片。(2)其次，我们将考虑空间扩展系统，以了解空间结构是否以及如何影响合作行为。我们将研究如何动态和监管的公共产品，以及异质性细菌的流动性的额外影响，影响合作行为的出现。我们的理论研究将依赖于晶格气模型，我们将采用随机模拟和分析方法进行分析。实验将在两种不同的环境中使用生产者/非生产者共培养物进行：一个固定的空间环境，不连续地扩展到新的地点，以及一个结构化的环境，允许公共物品和细胞的连续传播。在不同的生态条件下，分析共文化在时空上的发展。

The emergence of cooperative traits (like production of public goods) in microbial populations and their maintenance in the presence of free-riders is a central problem in evolutionary biology. In the first funding period, our focus was on the effect of demographic noise on growth dynamics and composition of cooperative bacterial populations under non-selective and selective conditions, combining experiments and theory. We showed that under non-selective conditions, growing populations never fixate to a trait, but adjust to a random steady state composition. In selective conditions, we experimentally validated our theoretical prediction that demographic noise leads to a transient increase in the fraction of public good producers in an ensemble of populations. To this end, we established a synthetic ecosystem and identified experimental conditions for cooperative behavior in Pseudomonas populations. Moreover, we showed that the expression of pyoverdine synthesis genes is phenotypically heterogeneous in a Pseudomonas population, and is modulated by iron availability. In the upcoming funding period, we intend to broaden the scope of the project and proceed along two main lines of research. (1) First, we will develop a more mechanistic molecular understanding of gene regulatory mechanisms underlying pyoverdine production and consumption, as well as its effect on the growth rate of producer and non-producer strains. Previous theoretical models partially neglected the effects of accumulated pyoverdine and growth phase on siderophore production. We will extend these models to account for this feature and perform a quantitative analysis of the impact of external pyoverdine on growth dynamics of producer and non-producer strains. Moreover, we plan to unravel the molecular mechanisms of pyoverdine production and regulation in P. putida. Specifically, we will analyze the presumed individual regulatory circuits and relate their activity to the metabolic state and pyoverdine production under various conditions of iron availability. These analyses will provide a comprehensive picture of the regulatory network and information on cell behavior in different environments. (2) Second, we will consider spatially extended systems to understand whether and how spatial structuring impacts cooperative behavior. We will investigate how the additional effects of dynamics and regulation of the public goods, and heterogeneity in bacterial mobility affect the emergence of cooperative behavior. Our theoretical studies will rely on lattice gas models, which we will analyze employing stochastic simulations and analytic approaches. Experiments will be performed with producer/non-producer co-cultures in two distinct settings: a fixed spatial environment with discontinuous expansion to new sites, and a structured environment allowing continuous spreading of public good and cells. The development of the co-culture in space and time will be analyzed in various ecological conditions.