NSF Engineering Research Center for Precision Microbiome Engineering (PreMiEr)

微生物已经定居并适应了地球上的几乎所有环境，包括人类创造的建筑环境，比如我们居住的房屋和给我们带来饮用水的管道。众所周知，微生物群落或微生物群对人类健康有直接影响。特别是建筑环境中的微生物组，通过与人类微生物组的相互作用，其在人类健康中的关键作用已得到越来越多的认识。然而，尽管有这些知识，还没有系统的基础设施来解释微生物系统如何适应和生长在建筑环境中，阻碍了我们诊断建筑环境健康和利用这些微生物群固有力量的能力。精密微生物组工程工程研究中心（PreMiEr）将创建基于微生物组的诊断工具，并开发微生物组工程方法，以监测和操作建筑环境，最大限度地保护人类健康。根据社会需求和研究利益相关者团队的信息，PreMiEr的研究设计将致力于防止传染性病原体的传播，促进有益微生物的定植，并制定控制流行病和抗生素耐药性的策略——这些现象已导致全球超过600万人死亡（截至2022年6月），仅去年一年就给全球经济造成了约8万亿美元的损失。作为其研究愿景的一部分，PreMiEr将创建多样化和包容性的跨学科研究和培训中心，工程师、微生物学家、社会科学家和伦理学家将与理论家、模型构建者和计算科学家一起开发技术，以安全、可持续和负责任的方式实现变革性的工程发现。我们设计微生物组的能力需要对群落生态学的概念有基本的了解，并有能力跟踪、控制和模拟这些相互作用。为了将微生物组工程应用到现实世界的系统中，社区级的交互必须集成到一个全面的、可扩展的建模框架中，这需要在模型测试平台中进行迭代评估和验证。PreMiEr的研究机构旨在对这些层次和功能产生基本的理解，最终形成一个框架，使智能和健康的建筑环境的生物设计成为可能。PreMiEr将利用高通量基因组测序、高分辨率质谱分析、计算性能和统计建模方面的先进技术来揭示以前未知的机制相互作用。将开发使能技术，以检测和确定建筑环境中的相互作用，包括探测微生物暗物质的方法，以开发建筑环境健康诊断工具；靶向递送所需遗传特征和微生物载体的方法；用于精细原位功能调谐的工具；以及可预测的可扩展统计微生物组工程模型，该模型考虑了高维性、稀疏性和异质性。这些新技术元素将使我们能够测试与微生物组组装和功能相关的假设。重要的是，通过将社会科学家和伦理学家纳入总理的研究框架，非社会科学家的工作将通过考虑他们的微生物组工程发现的伦理、社会和政策影响而得到通知。通过严格的评估和不断改进课程，以及旨在支持融合文化和传播研究成果的制度实践，PreMiEr将促进国内培训的最佳实践。PreMiEr ERC将包括有针对性地从代表性不足的群体中招募学员，建立与我国最大的HBCU的现有伙伴关系，并将在多学科的界面上提供沉浸式研究和培训，以应对复杂的挑战。PreMiEr将在技术和专业技能方面培养下一代多样化和高度积极性的工程师和科学家，以在新兴的微生物科学和工程领域竞争。最终，我们的工作将推进环境微生物组的合作和发现，以设计健康的建筑环境。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。

Microbes have colonized and adapted to most every environment on Earth, including the built environments that humans have created, such as the homes where we live and the pipes that bring us drinking water. It has been well established that microbial communities, or microbiomes, that colonize people have a direct influence on human health. The microbiome of the built environment, in particular, has gained increasing recognition for its key role in human health through its interaction with the human microbiome. However, despite this knowledge, no systematic infrastructure exists to decipher how microbial systems adapt to and grow within built environments, impeding our ability to diagnose built environment health and harness the power inherent to those microbiomes. The Engineering Research Center for Precision Microbiome Engineering (PreMiEr) will create microbiome-based diagnostic tools and develop microbiome engineering approaches to monitor and operate built environments that maximize human health protection. Informed by societal needs and research-stakeholder teams, PreMiEr’s research design will work to prevent the spread of infectious agents, promote the colonization of beneficial microorganisms, and lead to strategies for controlling pandemics and antibiotic resistance—phenomena that have led to over six million deaths worldwide (as of June 2022) and cost the global economy an estimated $8 trillion in the last year alone. Integral to its research vision, PreMiEr will create diverse and inclusive interdisciplinary research and training hubs where engineers, microbiologists, social scientists, and ethicists work alongside theorists, model builders, and computational scientists to develop technologies that enable transformative engineering discoveries in safe, sustainable and responsible ways.Our capacity to engineer microbiomes requires a fundamental understanding of concepts of community ecology and an ability to track, control, and model those interactions. To apply microbiome engineering to real-world systems, community level interactions must be integrated into a comprehensive, scalable modeling framework that requires iterative evaluation and validation in model testbeds. PreMiEr’s research organization is designed to generate fundamental understanding across these levels and functionalities, culminating in the development of a framework that enables the biodesign of smart and healthy built environments. PreMiEr will leverage advances in high-throughput genomic sequencing, high-resolution mass spectrometry, computational performance, and statistical modeling to unravel previously unknown mechanistic interactions. Enabling technologies will be developed to detect and define interactions in the built environment, including approaches that probe microbial dark matter for the development of built-environment health diagnostic tools; methods for targeted delivery of desired genetic features and microbial vectors; tools for fine in situ functional tuning; and predictive scalable statistical microbiome engineering models that consider high dimensionality, sparsity, and heterogeneity. These new technology elements will enable us to test hypotheses related to microbiome assembly and function. Importantly, by incorporating social scientists and ethicists into PreMiEr’s research framework, non-social scientists’ work will be informed by consideration of the ethical, societal, and policy implications of their microbiome engineering discoveries. Through rigorous evaluation and iterative refinement of curricula, and institutional practices designed to support a culture of convergence and the dissemination of findings, PreMiEr will contribute to best practices in domestic training. The PreMiEr ERC will include targeted recruitment of trainees from underrepresented groups, building upon existing partnerships with our nation’s largest HBCU, and will provide immersion in research and training at the interface of multiple disciplines to address complex challenges. PreMiEr will train the next generation of diverse and highly motivated engineers and scientists in technical and professional skills to compete in the emerging arenas of microbial science and engineering. Ultimately, our work will advance collaborations and discovery focused on environmental microbiomes to engineer healthy built environments.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.