EAGER: Investigating a Trojan Horse strategy to disrupt Saccharomyces biofilms

微生物是一种单细胞生物体，几乎在地球上的任何地方都可以找到，并且复杂地参与生物系统的功能。大多数微生物生活在复杂的群落中，参与从合作到致命战争的社会互动。当单个微生物聚集成一个群落（称为生物膜）并生产供所有人使用的产品时，就会发生一种类型的合作，作为回报，微生物会受到外部环境压力的保护。生物膜容易受到“骗子”的影响，他们不做贡献，但从社区结构中受益。生物膜无处不在，在自然环境以及工业和医疗环境中都有发现，它们可能危及人类健康和福利。这项研究的目的是确定作弊微生物是否有可能破坏和破坏不受欢迎的生物膜群落。利用计算机模拟，这项研究将测试是否以及在什么条件下，引入一种产生致命毒素的“特洛伊木马”微生物可能会破坏生物膜群落的稳定性。然后将使用天然和工程酵母菌株测试模拟结果。这项研究的一个成果是，它将提供一个概念验证，证明社会进化理论如何用于生物膜引起问题的重要医疗和工业应用。该项目还将为本科生和研究生研究人员提供机会，以跨学科的方法来解决问题？从理论到模拟，再到用活的有机体进行的实验。像所有的合作群落一样，生物膜容易受到自私个体的入侵，这些个体从合作中受益，但不做贡献。因此，对微生物社会相互作用及其长期后果的研究可以更好地了解可能破坏这些社区稳定的过程。已经提出了一种这样的策略，即使用工程化的“特洛伊木马”菌株渗透生物膜，但没有用空间明确的模型或实验工作进行测试。在这个项目中，研究人员将首先采用基于个体的、空间上明确的随机模拟来模拟细胞与生物膜群落的相互作用。该模型将用于确定不同的社会策略如何影响多种细胞类型的生长和分布，并研究模型参数如何影响特洛伊木马策略的有效性，以防止生物膜生长和破坏已经建立的社区。该项目的第二步是测试具有模拟策略的生物体是否可以破坏生物膜。将利用芽殖酵母酿酒酵母的天然和工程菌株。作为这项研究的一部分，将在一组天然酵母菌株中评估社会表型（生物膜形成和毒素产生）的适应性效应。该研究的成功完成将有助于开发社会进化研究的主要模式生物，并探索将社会进化理论应用于医学和工业应用的可能性。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbes are single-celled organisms found nearly everywhere on earth and are intricately involved in the functioning of biological systems. Most microbes live in complex communities and engage in social interactions ranging from cooperation to lethal warfare. One type of cooperation occurs when individual microbes aggregate into a community, known as a biofilm, and produce goods to be used by all, and in return, receive protection from external environmental stresses. Biofilms are susceptible to "cheaters" who do not contribute but benefit from the community structure. Biofilms are ubiquitous and are found both in natural environments and in industrial and medical settings, where they can endanger human health and welfare. The goal of this research is to determine whether it is possible for cheater microbes to disrupt and destroy undesirable biofilm communities. Using computer simulations, the research will test whether, and under what conditions, introducing a "Trojan Horse" microbe that produces a lethal toxin could destabilize a biofilm community. The results of the simulations will then be tested using natural and engineered yeast strains. One outcome of this research is that it will provide a proof-of-concept that demonstrates how social evolution theory could be used in important medical and industrial applications where biofilms cause problems. This project will also provide the opportunity for undergraduate and graduate researchers to be trained in an interdisciplinary approach to problem solving? from theory, to simulations, to experiments with living organisms.Like all cooperative communities, biofilms are susceptible to invasion by selfish individuals who benefit from cooperation, but do not contribute. Therefore, the study of microbial social interactions and their long-term consequences could lead to a better understanding of processes that can destabilize these communities. One such strategy, which would use an engineered "Trojan Horse" strain to infiltrate a biofilm, has been proposed, but not tested with a spatially explicit model or experimental work. In this project researchers will first employ individual-based, spatially explicit, stochastic simulations to model cells interacting a biofilm community. The model will be used to determine how different social strategies influence the growth and distribution of multiple cell types and to investigate how modeled parameters affect the effectiveness of a Trojan Horse strategy to prevent biofilm growth and disrupt an already established community. The second step of the project is to test whether living organisms with the simulated strategies can disrupt biofilms. Natural and engineered strains of the budding yeast Saccharomyces cerevisiae will be utilized. As part of this research, the fitness effects of social phenotypes (biofilm formation and toxin production) will be assessed in a panel of natural yeast strains. The successful completion of this research will contribute to developing a major model organism for social evolutionary studies, as well as explore the possibility of applying social evolution theory to medical and industrial applications.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.