EAGER: Actuation of Synthetic Cells Via Proto-Flagellar Motors

EAGER：通过原鞭毛马达驱动合成细胞

• 批准号: 2039277
• 负责人: Richard Murray
• 金额: $ 30万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2039277&HistoricalAwards=false
• 关键词: EAGER; Actuation; Synthetic; Cells; Via

This is a project that focuses on the development of functioning molecular motors for micron-scale synthetic cells, demonstrating mechanisms for motility in (synthetic) cellular systems. Recent advances in the fields of synthetic biology and molecular sciences have substantially advanced the ability to produce genetically-programmed synthetic cells and multicellular machines from molecular components. These efforts provide techniques for the bottom-up construction of cell-like systems that can provide scientists with new insights into how natural cells work, harness the power of biology to create nanoscale, biomolecular machines, and provide an exciting pathway for exploration of the Rules of Life. This project considers the ‘actuation’ subsystem of a synthetic cell, with the goal of allowing expression of membrane-integrated actuation complexes that can serve as a starting point to modulate the motility of the cell. The project engages undergraduate students from the Summer Undergraduate Research Fellowship program at California Institute of Technology and establishes collaborations between the US Build-A-Cell consortium and Imperial College, London, that includes personnel exchanges to build stronger international ties.To demonstrate the ability to express actuation complexes capable of modulating motility, this project (i) creates and optimizes vesicles with reconstituted transmembrane complexes (proto-flagella) that can eventually drive motility and (ii) engineers new vesicle systems that rely on TX-TL for the synthesis of the soluble and membrane proteins needed for motility. The project team redefines the state of the art by driving a step change in the type and complexity of behavioral modules that can be introduced into synthetic cells. Reconstituting membrane proteins provides new insights into the biological processes that underlie mechanisms for motility in microorganisms. In conjunction, the project develops generic methodologies for achieving in vesicle genetic control of membrane proteins, using proto-flagella as a test case.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.

该项目专注于开发微米级合成细胞的功能性分子马达，展示（合成）细胞系统的运动机制。合成生物学和分子科学领域的最新进展极大地提高了遗传生产的能力。 -由分子成分组成的编程合成细胞和多细胞机器，这些努力提供了自下而上构建类细胞系统的技术，可以为科学家提供关于自然细胞如何工作的新见解，利用生物学的力量来创建纳米级生物分子机器。 ， 和为探索生命规则提供了一条令人兴奋的途径。该项目考虑了合成细胞的“驱动”子系统，其目标是允许膜集成驱动复合物的表达，该复合物可以作为调节细胞运动的起点。该项目吸引了加州理工学院暑期本科生研究奖学金计划的本科生，并在美国 Build-A-Cell 联盟和伦敦帝国理工学院之间建立了合作关系，其中包括人员交流，以建立更牢固的国际联系。为了证明表达能够调节运动的驱动复合物的能力，该项目 (i) 创建并优化具有重构跨膜复合物（原鞭毛）的囊泡，最终可以驱动运动；(ii) 设计依赖 TX-TL 的新囊泡系统运动所需的可溶性和膜蛋白的合成该项目团队通过推动行为模块的类型和复杂性的逐步变化重新定义了现有技术。重组膜蛋白为微生物运动机制的生物过程提供了新的见解，该项目以原鞭毛为测试案例，开发了实现膜蛋白囊泡遗传控制的通用方法。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。