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

合成生物学(SynBio)是工程学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建造有用的新生物系统，如代谢途径。SynBio还可以揭示生物系统背后的深层运作原理--“生命法则”。这是通过应用构建-学习哲学来实现的，即：(I)基于规则的当前知识设计和构建生物系统；(Ii)如果系统没有如预测的那样运行，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智力和实践潜力，但它在植物生物学方面进展缓慢，而且SynBio的培训历来集中在工程学校，那里的女性和其他群体的比例明显偏低。因此，迫切需要将SynBio纳入主流植物新陈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新陈代谢的规则。该项目将相应地利用三所领先的植物科学大学互补的SynBio优势来设计一个三校区的博士培训和研究计划，以确定指导新代谢途径工程的规则。该项目将在虚拟研讨会中设计，每个校园一个。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，以纠正工程学领域的性别不平衡。这些研讨会还将帮助规划一个重要的2021年植物合成生物会议，由Co-Pi Lenaghan主持。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，并改变植物的改良，特别是代谢性状的改良。然而，也许是因为它的根源是化学工程，合成生物革命几乎还没有达到植物科学。为了解决针对植物科学家的SynBio博士培训的严重不足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一起，汇集他们的互补专业知识，以设计一个协调的三个校区的SynBio博士培训和研究计划。该项目将举办三个虚拟研讨会(每所大学主办一个)，以计划一个SynBio研究生证书和一个协调一致的研究计划，以定义生命规则，这些规则(I)预测在微生物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)使酶的数量、化学计量比和酶活性的时间得到调整，以确保新的多酶途径在植物中有效运行。在证书计划中，每所大学将在各自的专业领域教授在线翻转课堂课程，并将聘请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、新陈代谢工程、合成调节电路和定向进化。讲习班还将规划招募妇女的战略。最后，研讨会将帮助规划美国植物生物学家协会2021年合成生物大会，由Co-Pi Lenaghan担任主席。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.