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

合成生物学（SynBio）是工程与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还能揭示构成生物系统的深层运作原理——“生命法则”。这是通过应用构建学习的理念来实现的，即(i)根据当前的规则知识设计和构建生物系统；（ii）如果系统不像预期的那样运行，诊断原因，从而加深对规则的了解。尽管SynBio在代谢工程方面具有强大的知识力量和实际潜力，但它在植物生物学方面进展缓慢，而且SynBio的培训一直集中在工程学院，而女性和其他群体的代表性明显不足。因此，迫切需要将SynBio引入主流的植物代谢研究和多样化的培训，并利用SynBio的构建学习理念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项目，以确定指导新型代谢途径工程的规则。该项目将在虚拟研讨会中进行设计，每个校园都有一个研讨会。设计目标将是：(1)将基本的工程技能和在SynBio公司的实习纳入博士培训，从而获得大学间的研究生研究证书；(2)制定招聘女性的战略，以纠正工程领域的性别失衡。这些研讨会还将帮助规划2021年植物合成生物大会（Plant SynBio Conference），由Lenaghan共同主持。合成生物学（SynBio）有能力将生物学从一门描述性的学科转变为一门规范性的学科，并改变植物的改良，特别是代谢性状。然而，也许因为它的根源是化学工程，SynBio革命还没有触及到植物科学。为了解决SynBio植物科学家博士培训的严重短缺，以及女性在该领域的代表性不足，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聚集在一起，汇集他们互补的专业知识，设计一个协调的SynBio三校区博士培训和研究计划。该项目将举办三次虚拟研讨会（每所大学主办一次），以规划SynBio的研究生证书和一项协调一致的研究计划，以确定生命规则(i)预测在微生物SynBio平台上开发的酶和代谢途径将如何转移到植物中，以及（ii）能够调整酶活性的数量，化学计量学和时间，以确保植物中新的多酶途径的有效运作。在认证项目中，各大学将根据学生的专业领域开设在线翻转课堂课程，并聘请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。讲习班还将规划招募妇女的战略。最后，这些研讨会将帮助规划美国植物生物学家协会2021年的SynBio会议，Lenaghan将担任联席主席。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。

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.