BII-Design: Using Synthetic Biology to Discover Cross-Kingdom Metabolic Rules of Life

BII-Design：利用合成生物学发现跨领域的生命代谢规则

• 批准号: 2320270
• 负责人: Scott Lenaghan
• 金额: $ 19.99万
• 依托单位: University of Tennessee Institute of Agriculture
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2320270&HistoricalAwards=false
• 关键词: BII; Design; Using; Synthetic; Biology

Synthetic biology (SynBio) is a revolutionary combination of engineering and life sciences. It empowers investigators to design and build from the ground up useful new biological systems such as metabolic pathways. SynBio can also uncover the deep operating principles that underlie biological systems – the ‘Rules of Life’. This is done by applying the build-to-learn philosophy, i.e. (i) design and construct biosystems based on current knowledge of the Rules; (ii) if the systems don’t perform as predicted, diagnose why and thus deepen knowledge of the Rules. Despite its intellectual power and practical potential in metabolic engineering, SynBio has been slow to reach plant biology and SynBio training has historically been concentrated in engineering schools where women and other groups are notably underrepresented. There is consequently an urgent need to bring SynBio into mainstream plant metabolism research and diversified training, and to use SynBio’s build-to-learn philosophy to define Rules for redesigning plant metabolism. This project will accordingly harness the complementary SynBio strengths of three leading plant science universities to design a tri-campus PhD training and research program to define Rules to guide engineering of novel metabolic pathways. The project will be designed in virtual workshops, one hosted by each campus. Design goals will be to (i) integrate basic engineering skills and internships in SynBio companies into PhD training, leading to an interuniversity graduate research certificate, and (ii) develop strategies to recruit women to redress the gender imbalance in engineering. The workshops will also help plan a major 2021 Plant SynBio Conference, which Co-PI Lenaghan will chair. Synthetic biology (SynBio) has the power to change biology from a descriptive to a prescriptive discipline and to transform plant improvement, particularly of metabolic traits. However, perhaps because its roots are in chemical engineering, the SynBio revolution has barely reached plant science yet. To address the critical shortage of SynBio PhD training for plant scientists, and the underrepresentation of women in the field, plant scientists and metabolic engineers at three major plant science universities (University of Florida, University of Tennessee, and Purdue University) have come together in this project to pool their complementary expertise to design a coordinated three-campus PhD training and research program in SynBio. The project will hold three virtual workshops (one hosted by each university) to plan a graduate certificate in SynBio and a concerted research plan to define Rules of Life that (i) predict how well enzymes and metabolic pathways developed in microbial SynBio platforms will transfer to plants, and (ii) enable the amount, stoichiometry, and timing of enzyme activity to be adjusted to assure efficient operation of new multienzyme pathways in plants. In the certificate program, online flipped-classroom courses will be given in their areas of expertise by each university and SynBio companies will be recruited to host internships for students. Courses will cover basic coding, engineering principles, metabolic engineering, synthetic regulatory circuits, and directed evolution. The workshops will also plan strategies to recruit women. Lastly, the workshops will help plan the American Society of Plant Biologists’ 2021 SynBio Conference, which Co-PI Lenaghan will chair.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.

合成生物学（SynBio）是工程和生命科学的革命性结合。它使研究人员能够从头开始设计和构建有用的新生物系统，如代谢途径。SynBio还可以揭示生物系统背后的深层运作原则-“生命规则”。这是通过应用构建学习哲学来完成的，即（i）基于规则的当前知识设计和构建生物系统;（ii）如果系统没有按照预测执行，则诊断原因，从而加深规则的知识。尽管SynBio在代谢工程领域拥有强大的智力和实践潜力，但它在植物生物学方面的进展缓慢，而且SynBio的培训历来集中在女性和其他群体代表性明显不足的工程学校。因此，迫切需要将SynBio纳入主流植物代谢研究和多样化培训，并使用SynBio的构建学习哲学来定义重新设计植物代谢的规则。因此，该项目将利用三所领先的植物科学大学的互补SynBio优势，设计一个三校区的博士培训和研究计划，以定义指导新代谢途径工程的规则。该项目将在虚拟研讨会上进行设计，每个校区主办一个研讨会。设计目标将是（i）将基本工程技能和SynBio公司的实习纳入博士培训，从而获得大学间研究生研究证书，以及（ii）制定招聘女性的战略，以纠正工程领域的性别不平衡。这些研讨会还将帮助规划2021年植物SynBio会议，Co-PI Lenaghan将主持该会议。 合成生物学（SynBio）有能力将生物学从描述性学科转变为规范性学科，并改变植物改良，特别是代谢性状。然而，也许是因为它的根源是化学工程，SynBio革命几乎还没有达到植物科学。为了解决植物科学家的SynBio博士培训的严重短缺，以及该领域女性代表性不足的问题，三所主要植物科学大学（佛罗里达大学，田纳西大学和普渡大学）的植物科学家和代谢工程师在这个项目中走到了一起，汇集他们的互补专业知识，设计一个协调的三校区SynBio博士培训和研究计划。该项目将举办三个虚拟研讨会（每个大学主办一个）计划SynBio的研究生证书和一个共同的研究计划，以定义生命规则，（i）预测微生物SynBio平台中开发的酶和代谢途径将如何转移到植物中，以及（ii）使数量，化学计量，以及调节酶活性的时间以确保植物中新的多酶途径的有效操作。在证书课程中，每所大学将在其专业领域提供在线翻转课堂课程，并将招募SynBio公司为学生提供实习机会。课程将涵盖基本编码，工程原理，代谢工程，合成调控电路和定向进化。讲习班还将规划征聘妇女的战略。最后，研讨会将帮助规划美国植物生物学家学会2021年SynBio会议，联合PI Lenaghan将主持该会议。该奖项反映了NSF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。