CAREER: Real-time evolution in host-pathogen networks

从抗药性细菌的出现到病毒病原体的宿主转换，我们面临的许多传染病问题本质上都是进化的。理论工作表明，病原体的传染性和毒力随着宿主之间移动和接触的方式(社会接触网络)而演变。然而，检验这些预测的实验工作相对较少。该项目将数学和计算方法与实时微生物进化相结合，以探索网络结构如何影响宿主-病原体的进化。实验方法涉及一个由细菌(宿主)及其病毒(病原体)组成的模型社区。这些微生物被嵌入到亚种群阵列中，并使用高通量机器人来控制亚种群之间的移动。随着亚种群网络结构的变化，可以在遗传和生理水平上实时跟踪病原菌及其寄主的变化。主要的研究人员将集中在社会网络结构如何影响病原体生命周期的不同组成部分的进化(例如，宿主进入和退出)、可进化性？病原体的特性(即其快速性状变化的倾向)，以及寄主对病原体的反应进化，反之亦然。这个项目的重点是进化。更广泛地说，进化论是现代生物学的中心支柱。尽管如此，公众对美国的进化论仍普遍持怀疑态度。这种怀疑在一定程度上是由对进化论原理的基本误解造成的。在课堂上，这种情况反映了未能传达进化论的核心方面，它的科学基础，以及它与公共利益的相关性。主要研究人员将设计并公开传播一套新的实时进化模块，用于本科实验室课程。重点将是疾病的进化，使用上述无害的微生物宿主-病原体系统。这些单元将通过亲身实践和基于探究的实验来说明进化过程。此外，首席研究员将与其他学科(包括生物工程、癌症研究、基因组科学、渔业和电气工程)的研究人员合作，设计一个长达一年的实验进化序列。在这个序列中，学生们将提出并测试他们自己的进化假说。在这个过程中，学生将了解科学研究的性质和有效的实验方法。该项目的教育和研究目标将直接涉及研究生和本科生，并将特别努力使代表性不足的群体参与进来。

From the advent of antibiotic resistant bacteria to host switching in viral pathogens, many of the problems we face with infectious disease are evolutionary in nature. Theoretical work suggests that pathogen infectivity and virulence evolve in response to the manner in which hosts move and contact one another (the ?social contact network?). However, there has been relatively little experimental work to test these predictions. This project combines mathematical and computational approaches with real-time microbial evolution to explore how network structure influences host-pathogen evolution. The experimental approach involves a model community comprised of bacteria (hosts) and their viruses (pathogens). The microbes are embedded in subpopulation arrays and a high-throughput robot is used to control movement between subpopulations. As the subpopulation network structure is varied, the changes in both the pathogen and its host are tracked in real time at genetic and physiological levels. The primary investigator will focus on how the structure of the social network influences the evolution of different components of the life cycle of the pathogen (e.g., host entry and exit), the ?evolvability? of the pathogen (i.e., its proclivity for rapid trait change), and the evolution of the host in response to the pathogen and vice versa. The focus of this project is evolution. More generally, the subject of evolution occupies a central pillar of modern biology. Nonetheless, there is widespread public skepticism about evolution in the United States. This doubt is fueled, in part, by basic misunderstanding of evolutionary principles. In the classroom, this situation reflects a failure to communicate central aspects of evolutionary theory, its scientific foundation, and its relevance for the public good. The primary investigator will design and publicly disseminate a set of new real-time evolution modules for use in undergraduate laboratory courses. The focus will be disease evolution, using the innocuous microbial host-pathogen systems described above. These modules will illustrate evolutionary processes through hands-on and inquiry-based experiments. Additionally, the primary investigator will design a year-long sequence in experimental evolution in collaboration with researchers from other disciplines (including bioengineering, cancer research, genome sciences, fisheries, and electrical engineering). In this sequence, students will pose and test their own evolutionary hypotheses. In the process, students will learn about the nature of scientific research and effective experimental methodology. Both educational and research aims of this project will directly involve graduate and undergraduate students and special efforts will be taken to involve underrepresented groups.