UKRI/BBSRC-NSF/BIO: Community-dependent CRISPR-cas evolution and robust community function

UKRI/BBSRC-NSF/BIO：群落依赖性 CRISPR-cas 进化和强大的群落功能

• 批准号: 2321502
• 负责人: Samuel Brown
• 金额: $ 83.4万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2321502&HistoricalAwards=false
• 关键词: UKRI; BBSRC; NSF; BIO; Community; UKRI; BBSRC; NSF; BIO; Community

Microbiome research has produced an incredible inventory of data from diverse human and environmental samples. The field continues to implicate microbiomes (microbial communities) as potentially key causal agents in many biological processes governing human and environmental health. A major challenge for the field is to move beyond correlative approaches and to establish mechanistic and quantitative understanding of the forces shaping the dynamics and functions of microbiomes. Rationally designed and experimentally assembled ‘synthetic microbiomes’ offer an exciting avenue to decipher basic rules of microbial organization and engineer novel microbial solutions to pressing applied societal challenges. Yet, the robustness of synthetic microbiomes to environmental perturbations remains relatively untested. A major class of microbiome perturbation stems from assault by parasites of microbes, such as bacteriophage viruses (phages). This project investigates how defined microbiomes respond to viruses on both short timescales (via behavioral shifts) and longer timescales (via ecological and evolutionary shifts). Using a combination of theory and experiment, the project tests the hypothesis that robust microbiome functions are predictably promoted by microbial communication systems, and costs of virus resistance. The project holds broader impact through multiple societally relevant outcomes, spanning scientific literacy, research participation, STEM education and microbiome management. Individual species commonly evolve resistance to phages by modifying or entirely deleting the surface receptor used by the phage. This can have substantial impacts on the functional capacities and species interactions of the bacterium, due to the importance of surface factors in mediating environmental interactions. From a synthetic community perspective, surface factor modifications in response to phage exposure risk damaging the functional capacities of the community. Bacteria can also evolve resistance to phages via CRISPR-Cas, leaving the functional capacity of the cell intact, yet this pathway of acquired resistance is rarely seen in a lab setting. The paucity of lab CRISPR-Cas evolution presents a challenge to the understanding of CRISPR-Cas as a primary mechanism of acquired resistance. This project hypotheses that CRISPR-Cas immunity acquisition is an emergent property of intra- and inter-specific cell-cell signaling mechanisms and community-dependent fitness costs, which together promote robust community functioning. This project holds significance by identifying general principles, math models and tools for the design of synthetic microbial communities that are functionally robust against phage attack. These tools in turn promote microbiome-assisted societal goals for environmental health, human health and industry in applied settings where phage exposure is inevitable.This collaborative US/UK project is supported by the US National Science Foundation (NSF) and the UK Biotechnology and Biological Sciences Research Council (BBSRC), where NSF funds the US investigator and BBSRC funds the partners in the UK.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.

微生物组研究产生了来自潜水员和环境样本的数据的库存。该领域继续在许多涉及人类和环境健康的生物学过程中，将微生物组（微生物群落）作为潜在的关键因果剂。该领域的一个主要挑战是超越相关方法，并建立对塑造微生物组动力学和功能的力的机械和定量理解。合理设计和实验组装的“合成微生物组”为破译微生物组织和工程师新型微生物解决方案的基本规则提供了令人兴奋的途径，以应对应用社会挑战。然而，合成微生物组对环境扰动的鲁棒性仍然相对未经测试。一类主要的微生物组扰动植物遭到微生物寄生虫的攻击，例如噬菌体病毒（噬菌体）。该项目调查了定义的微生物组如何对短时标（通过行为变化）和更长的时间尺度（通过生态和进化变化）响应病毒。通过理论和实验的结合，该项目检验了以下假设：鲁棒微生物组功能可以通过微生物通信系统和病毒抗性的成本来预测。该项目通过多种与社会相关的成果，涵盖科学素养，研究参与，STEM教育和微生物组管理的影响更大。单个物种通常通过修改或完全删除噬菌体使用的表面受体来发展对噬菌体的抗性。由于表面因素在介导环境相互作用中的重要性，这可能会对细菌的功能能力和物种相互作用产生重大影响。从合成社区的角度来看，响应噬菌体暴露的表面因子修改可能会损害社区的功能能力。细菌还可以通过CRISPR-CAS进化对噬菌体的抗性，使细胞的功能能力完好无损，但是在实验室环境中很少看到这种获得的抗性途径。 Lab CRIS-CAS进化的稀缺性对理解CRISPR-CA的理解是获得抗药性的主要机制的挑战。该项目假设CRISPR-CAS免疫获取是内部和特异性细胞间信号机制和社区依赖性健身成本的紧急特性，共同促进了强大的社区功能。该项目通过确定用于设计合成微生物群落的一般原理，数学模型和工具，具有在功能上可靠的噬菌体攻击。 These tools in turn promote microbiome-assisted social goals for environmental health, human health and industry in applied settings where phage exposure is inevitable.This collaborative US/UK project is supported by the US National Science Foundation (NSF) and the UK Biotechnology and Biological Sciences Research Council (BBSRC), where NSF funds the US investigator and BBSRC funds the partners in the UK.This award reflects NSF's法定使命，并通过评估诚实地认为，使用基金会的智力优点和更广泛的影响审查标准。