CAREER: Mechanism of Metallic Conductivity in Bacterial Pili Filaments

电子在生物分子和材料中的运动是许多物理、化学和生物过程以及电子工业的核心。PI发现，普通土壤细菌的蛋白质细丝可以像金属系统一样移动电子。在这个CAREER项目中，PI将确定这一过程背后的机制，这种过程发生在前所未有的距离上。研究结果可以应用于环境、生物能源和微电子领域。PI将把这项研究整合到一系列教育活动中，以激励和训练下一代跨学科学生解决具有挑战性的问题。PI将利用他自己在生物物理学、结构和分子生物学方面的训练，以及他在技术创新和创业方面的经验，为所有层次的学生提供服务。具体而言，PI将首先为本科生和研究生开发一个新的跨学科课程，介绍传统课程中未涉及的物理、化学和生物交叉领域的关键概念。其次，项目负责人将利用纽黑文公立学校（New Haven Public School）教师的反馈，设计有关细菌驱动燃料电池科学的动手实验活动，该学校主要为少数族裔学生提供服务。第三，PI将通过基于First Glance和Proteopedia的用户友好软件传播分子结构。第四，PI将通过与耶鲁大学科学教育助理院长和当地社区和外展活动协调员密切合作，增加代表性不足和少数族裔学生对研究的参与。因此，这个CAREER项目将在物理、化学和生物学的界面上整合高度跨学科的研究，并为各个层次的学生提供多样化的教育计划。电子传递是许多生命过程的基础。现有的生物电子转移模型主要依赖于隧道和跳跃机制，这些机制仅限于几纳米，而金属电导率被认为是不可能在蛋白质中实现的。这些模型无法解释细菌传输电子的非凡能力，这种传输能力是细菌自身大小的1万倍。通过引入通过紧密堆叠的芳香残基来解释毛蛋白高导电性的离域传导的新概念，耶鲁大学的这个CAREER项目提案将通过建立细胞外电子传递的机制框架来扩大生物物理学的知识范围。该项目的总体目标是确定土壤细菌的细胞外电子转移机制，这种转移发生在生物学上前所未有的速度和距离。在该项目发现硫还原地杆菌菌毛蛋白丝具有与金属聚合物相似的电学特性的基础上，本项目旨在确定金属电导率的结构、分子和生物物理机制。首先，PI将确定毛中导致电子离域的关键微观传输参数。其次，PI将可视化毛中驱动电子传递的构象变化。第三，PI将使用Cryo-EM获得毛的近原子分辨率结构。这个项目的成功可以为调节我们环境的微生物物种多样性的代谢和交流提供前所未有的新见解，并且对生物能源和生物燃料战略非常重要。通过导电菌毛的工程微生物相互作用可以潜在地控制它们的生理和生态。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。

The movement of electrons in biomolecules and materials is central to many physical, chemical and biological processes as well as to electronics industry. The PI has found that protein filaments of common soil bacteria can move electrons similar to metallic systems. In this CAREER Project, the PI will identify the mechanism underlying this process that occurs over unprecedented distances. The results of the research could have applications in environmental, bioenergy, and microelectronics applications. The PI will integrate this research into a range of educational activities that will inspire and train the next-generation of interdisciplinary students to tackle challenging problems. The PI will draw from his own training in biophysics and structural and molecular biology as well as his experience in technology innovation and entrepreneurship to reach students at all levels. Specifically, the PI will first develop a new cross-disciplinary curriculum for undergraduate and graduate students to introduce key concepts at the intersection of physics, chemistry and biology that are not covered in traditional courses. Second, the PI will design hands-on laboratory activity on the science of bacteria-powered fuel cells, using the feedback from the teachers of New Haven Public School that primarily serve minority students. Third, the PI will disseminate molecular structures through a user-friendly software based on First Glance and Proteopedia. Fourth, the PI will increase participation of underrepresented and minority students into research by working closely with the Yale assistant dean of science education and the coordinator for local community and outreach events. Thus, this CAREER project will integrate highly interdisciplinary research at the interfaces of physics, chemistry and biology with a diverse educational program reaching students at all levels.Electron transfer is fundamental to many life processes. Existing models of biological electron transfer rely primarily on tunneling and hopping mechanisms that are limited to few nanometers, and metallic conductivity has been considered impossible in proteins. These models cannot explain the remarkable capacity by bacteria to transport electrons over centimeters, 10,000 times their size. By introducing a new concept of delocalized conduction via closely stacked aromatic residues that can account for high conductivity in pili proteins, this CAREER project at Yale University proposal will expand the intellectual range of biophysics by building a mechanistic framework for extracellular electron transport. The overall goal of this project is to identify the mechanism of extracellular electron transfer in soil bacteria that occurs at rates and distances unprecedented in biology. Building on the discovery by the PI that pili protein filaments of Geobacter sulfurreducens show electrical properties similar to metallic polymers, this project aims to identify the structural, molecular and biophysical mechanism of metallic conductivity. First, the PI will identify crucial microscopic transport parameters in pili that led to electron delocalization. Second, the PI will visualize conformational changes in pili that drive electron transport. Third, the PI will obtain near atomic-resolution structures of pili using Cryo-EM. The success of this project could provide unprecedented new insights into the metabolism and communication of a diversity of microbial species that regulate our environment and are important for bioenergy and biofuel strategies. Engineering microbial interactions via conductive pili could potentially offer control over their physiology and ecology.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.