Collaborative Research: Closed-loop control of microbial communities by integrating optogenetics and metabolite biosensing

合作研究：通过整合光遗传学和代谢物生物传感对微生物群落进行闭环控制

• 批准号: 2300239
• 负责人: Jose Avalos
• 金额: $ 94.78万
• 依托单位: Princeton University
• 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: 2023-06-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2300239&HistoricalAwards=false
• 关键词: Collaborative; Research; Closed; loop; control

Biotechnology is essential to the nation’s interest in scientific progress and maintaining world leadership in key strategic areas such as biomanufacturing, biomedical research, renewable energy, sustainability, and food production. While microbial bioprocesses are dominated by monocultures, utilization of synthetic microbial communities holds enormous potential for many applications in biotechnology, including production of high value chemicals. However, the lack of effective controls over key attributes of these communities impedes the development of this research field. This project will use metabolite biosensors and novel optogenetic growth control systems to modulate microbial community composition and to increase production of the desired chemical products. This project will generate new knowledge and methods to advance basic research in synthetic microbial communities and generate strategies for improved production of important chemicals. Moreover, this project will offer outstanding opportunities to engage high school, undergraduate, and graduate students in STEM education.The overall goal of this project is to integrate optogenetic controls and metabolite biosensing to achieve unprecedented automated dynamic regulation of microbial communities. Optogenetics offers the unique ability to control biological functions with light, which can be added or removed instantly and reversibly following any prescribed schedule. For this project, optogenetics will be used to modulate the growth of targeted microbes and ultimately to adjust contributions to bioproduction. Metabolite biosensing will provide instant feedback on the metabolic state of microbial communities to inform optogenetic actuators, establishing closed-loop feedback controls. This first-of-its-kind control system will be used to engineer interactions between members of microbial communities and their contributions towards collaborative biosynthetic pathways. It will also help identify the optimal community compositions throughout co-culture cultivation despite sup-optimal inoculums or system perturbations. Moreover, this project will explore the application of closed-loop controls in communities with different features, such as communities comprising members of the same or different species, containing linear or non-linear biosynthesis pathways, and capable of sensing biosynthetic pathway intermediates or final products. This project will open new opportunities to gain fundamental understanding of complex behaviors of synthetic microbial communities. This project is jointly supported by the Cellular and Biochemical Engineering, Biosensing and Biophotonics Programs in ENG/CBET, and the Systems and Synthetic Biology Program in BIO/MCB.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.

生物技术对于国家在生物制造、生物医学研究、可再生能源、可持续性和食品生产等关键战略领域的科学进步和保持世界领先地位至关重要。虽然微生物生物过程以单一培养为主，但合成微生物群落的利用具有巨大的潜力。然而，缺乏对这些群落关键属性的有效控制阻碍了该研究领域的发展。该项目将产生新的知识和方法，以推进合成微生物群落的基础研究，并制定改善重要化学品生产的策略。为高中生、本科生和研究生提供参与 STEM 教育的绝佳机会。该项目的总体目标是整合光遗传学控制和代谢物生物传感，以实现微生物群落的未发现的自动化动态调控。光遗传学提供了独特的控制能力。光的生物功能，可以按照任何规定的时间表立即和可逆地添加或删除，对于该项目，光遗传学将用于调节目标微生物的生长，并最终调整对生物生产的贡献。微生物群落的代谢状态，以通知光遗传学执行器，建立循环反馈控制，这种首创的控制系统将用于设计微生物群落成员之间的相互作用及其对封闭协作的贡献。它还将有助于确定整个共培养过程中的最佳群落组成，尽管存在次优接种或系统扰动，该项目将探索闭环控制在具有不同特征的群落中的应用，例如由成员组成的群落。相同或不同物种的，包含线性或非线性生物合成途径，并且能够感测生物合成途径中间体或最终产物。该项目将为获得对合成微生物的复杂行为的基本了解提供新的机会。该项目由 ENG/CBET 的细胞和生化工程、生物传感和生物光子学项目以及 BIO/MCB 的系统和合成生物学项目共同支持。该奖项反映了 NSF 的法定使命，经评估认为值得支持。利用基金会的智力优势和更广泛的影响审查标准。