BII: Host-Virus Evolutionary Dynamics Institute (HVEDI)

NSF生物整合研究所项目名为宿主-病毒进化动力学研究所（HVEDI），将作为一个多机构、多研究者的研究所建立，研究宿主-病毒在生命领域（细菌、古生菌、真核生物）的相互作用，目标是确定所有病毒都遵守的普遍“生命规则”。制定这样的生命规则将导致制定病毒学定律，从而可以预测病毒的毒性或减毒株的出现、物种跳跃事件、导致新病毒株的重组事件的倾向以及在不断变化的环境条件下病毒传播率的变化。除了科学之外，HVEDI是不同类型大学的合作，包括研究密集型机构（即卡内基研究1和2机构），主要的本科机构（PUIs），历史上的黑人学院和大学（hbcu）和西班牙裔服务机构（hsi）。因此，各种各样的教师和学生科学家将从事病毒学和病毒生态学的前沿研究，以实现项目的目标。这项工作的结果将大大有助于更好地理解病毒如何在特定条件下感染自然和新宿主。拓展和培训计划将惠及阿肯色州、缅因州和波多黎各的高中和社区学院，并将在这些地区和其他NSF EPSCoR辖区建立人力资源能力。虽然已经研究了特定病毒系统的宿主-病毒相互作用，但很少有研究试图比较跨生命领域的病毒-宿主动力学，以产生所有或大量不同病毒系统所遵循的基本生命规则。使用三种非裂解性、低毒力的双链（ds） DNA病毒系统——代表生命的每个领域（细菌、古生菌和真核生物）——将为这些核心病毒系统（CVS）中的每一个建立宿主-病毒相互作用特性模型。对所有三种CVS都适用的可数学表征的模式将被开发为建立宿主-病毒进化动力学的生命规则（RoL）的模型。然后将测试RoL是否适用于其他病毒系统（即比较系统），包括裂解系统和由RNA或单链DNA基因组组成的系统。这些比较系统将用于验证RoL模型，以制定一套病毒学定律。将实行三个层次的一体化。一级整合工作的重点是跨生物尺度（遗传学、组学、生理学、生态学）的整合，以模拟每个独立病毒系统的宿主-病毒相互作用动力学。第2级集成的重点是对CVS和比较病毒系统中发现的常见模式进行建模，以开发所有或大部分病毒都遵守的生命规则。3级整合的重点是将宿主-病毒相互作用的新生命规则应用于中生态、定向进化和更大规模（即生态系统/生态）应用。湿实验室实验将通过数学建模和基于计算机的宿主-病毒动力学模拟来支持。这项工作的结果将有助于更广泛地理解宿主切换、港口状态变化、毒力变化和其他相关现象。该奖项反映了美国国家科学基金会的法定使命，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。

The NSF Biology Integration Institute project entitled Host-Virus Evolutionary Dynamics Institute (HVEDI) will be established as a multi-institutional, multi-investigator institute to study host-virus interactions across domains of life (Bacteria, Archaea, Eukarya) with the goal of determining universal "rules of life" to which all viruses adhere. Developing such rules of life will lead to developing Laws of Virology that allow predictions for the emergence of virulent or attenuated strains of a virus, species jump events, the propensity for recombination events leading to novel virus strains, and changes in virus transmission rates under changing environmental conditions. Beyond the science, HVEDI is a collaborative of different university types, including research intensive institutions (i.e., Carnegie Research 1 and 2 institutions), predominantly undergraduate institutions (PUIs), Historically Black Colleges and Universities (HBCUs), and Hispanic-Serving Institutions (HSIs). Thus, a diverse array of faculty and student scientists will be engaged in cutting-edge research in virology and virus ecology toward achieving the objectives of the project. Results from this work will significantly contribute to a better understanding of how viruses may infect natural and novel hosts under select conditions. Outreach and training initiatives will benefit high schools and community colleges in Arkansas, Maine, and Puerto Rico and will build human resource capacity in these and other NSF EPSCoR jurisdictions.Although host-virus interactions have been studied for specific virus systems, few studies have sought to compare virus-host dynamics across domains of life towards generating fundamental rules of life to which all or large swaths of disparate virus systems adhere. Using three non-lytic, low-virulence double-stranded (ds) DNA virus systems - representing each domain of life (Bacteria, Archaea, and Eukarya) -host-virus interaction properties will be modeled for each of these core virus systems (CVS). Mathematically-characterizable patterns that hold for all three of the CVS will be developed as models towards establishing rules of life (RoL) for host-virus evolutionary dynamics. The RoL will then be tested for generalizability to other virus systems (i.e., comparator systems), including lytic systems and those comprised of RNA or single-strand DNA genomes. These comparator systems will be used to validate RoL models towards developing a set of Laws of Virology. Three levels of integration will be pursued. Level 1 integration efforts are focused on integrating across biological scales (genetics, -omics, physiological, ecological) towards modeling host-virus interaction dynamics for each independent virus system. Level 2 integration is focused on modeling common patterns found across the CVS and comparator virus systems towards developing rules of life to which all or a large swath of viruses adhere. Level 3 integration is focused on applying the emerging rules of life for host-virus interactions to mesocosm, directed evolution, and larger-scale (i.e., ecosystems/ecological) applications. Wet lab experimentation will be supported by mathematical modeling and computer-based simulations of host-virus dynamics. Results from this work will contribute to the broader effort of understanding host switch, changes in harbor state, changes in virulence, and other related phenomena.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.