EAGER: Actuation of Synthetic Cells Via Proto-Flagellar Motors

这是一个专注于开发用于微米级合成细胞的功能分子马达的项目，展示（合成）细胞系统中的运动机制。合成生物学和分子科学领域的最新进展大大提高了从分子成分生产遗传程序合成细胞和多细胞机器的能力。这些努力提供了自下而上构建细胞样系统的技术，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造纳米级的生物分子机器，并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，目标是允许表达膜集成驱动复合物，该复合物可以作为调节细胞运动的起点。该项目招收来自加州理工学院暑期本科生研究奖学金项目的本科生，并在美国build - a - cell联盟和伦敦帝国理工学院之间建立合作关系，包括人员交流，以建立更强的国际联系。为了证明表达能够调节运动性的驱动复合物的能力，该项目(i)用重建的跨膜复合物（原鞭毛）创建并优化了最终可以驱动运动性的囊泡，（ii）设计了依靠TX-TL合成运动性所需的可溶性和膜蛋白的新囊泡系统。项目团队通过推动可引入合成单元的行为模块的类型和复杂性的逐步变化，重新定义了技术的状态。重组膜蛋白为微生物运动机制的生物学过程提供了新的见解。同时，该项目开发了实现膜蛋白囊泡遗传控制的通用方法，使用原鞭毛作为测试案例。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。

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.