CAREER: Rapid continuous molecular evolution to create and probe protein-protein interactions

工程生物工具正在成为社会面临的一些最紧迫问题的关键解决方案。然而，设计生物组件以执行所需功能的挑战仍然是实现工程生物系统全部潜力的主要障碍。实验室分子进化——随着时间的推移改变分子结构和功能的迭代过程——为探索生物学提供了一个视角，也是创造功能分子的一个日益重要的实验室工具。该项目将通过开发和应用新的快速实验室进化系统来研究生物分子如何进化以相互作用。该项目将提供有关生物分子如何进化具有新功能的基础知识，重点关注与更广泛的生物群落相关的活动。此外，为这个项目创造的技术将为在实验室中利用分子进化作为设计工具带来新的方法。从该项目中收集的技术和基本见解将导致解决生物工程挑战的新方法。该项目将为芝加哥地区的学生和成年人提供教育机会，重点是利用工程生物学的主题来激发STEM参与。随着合成生物学在生物技术、农业和工业领域的不断普及，对创造和理解这些技术的生物成分的方法的需求也在增加。这个项目将在几个方面影响这些需求：1)研究分子相互作用的进化将导致如何更好地设计蛋白质的一般的，基本的见解。2)开发和利用新的分子进化技术将带来新的机会，将这些工具用于学术和商业目的的应用科学问题。3)从基础研究中进化出的蛋白质产物将为理解蛋白质结构/功能关系提供有用的工具。4)这项研究将为本科生和研究生提供一个肥沃的平台，使他们具备成为下一代合成生物学领导者所需的技能。5)该项目将在芝加哥南部开展工作，解释合成生物学的基本概念、目标和潜力，并激励当地年轻人进入STEM领域。6)该项目将与芝加哥的成人合作，向当地社区解释该项目，并提高人们对这些研究工作在未来几年将如何影响社会的认识。

Engineered biological tools are emerging as critical solutions to some of the most pressing issues facing society. However, challenges with designing biological components to perform desired functions remains a primary hurdle to realizing the full potential of engineered biological systems. Laboratory molecular evolution - the iterative process of changing the structure and function of a molecule over time - provides both a lens with which to probe biology and is an increasingly important laboratory tool for creating functional molecules. This project will study how biological molecules evolve to interact with one another by developing and applying new rapid laboratory evolution systems. This project will provide fundamental knowledge about how biomolecules evolve to have new functions, with a focus on activities of relevance to the broader biological community. Additionally, the technologies created for this project will lead to new approaches for harnessing molecular evolution in the laboratory as a design tool. The technologies and fundamental insights gleaned from this project will lead to new approaches to solve biological engineering challenges. This project will provide educational opportunities for students and adults in the Chicago area, with a focus on using the topic of engineering biology to inspire STEM participation.As synthetic biology continues to grow in prevalence in biotechnological, agricultural, and industrial arenas, the need for methods to create and understand the biological components of these technologies is also increasing. This project will impact these needs in several ways: 1) Studying the evolution of molecular interactions will lead to general, fundamental insights about how to better engineer proteins. 2) Developing and leveraging new molecular evolution technologies will lead to new opportunities to use these tools for applied scientific problems, both for academic and commercial purposes. 3) The evolved protein products from the fundamental studies in this work will serve as useful tools to understand protein structure/function relationships. 4) The research will provide a fertile platform for endowing undergraduates and graduate students with the skillsets needed to become the next generation of leaders in synthetic biology. 5) The project will involve work in the local Southside of Chicago to explain the fundamental concepts, goals, and potential of synthetic biology and motivate local youth to enter STEM fields. 6) The project will involve work with adult outreach in Chicago to explain the project to the local community and increase awareness about how these research efforts will impact society in the coming years.