RoL:EAGER: DESYN-C3. Bottom-up Synthetic Cells Capable of Darwinism, the Archetypal Trait of Life

有了这个奖项，化学部的生命过程化学（CLP）项目在应用分子进化基金会的Steven Benner博士的指导下，资助了可用于生物技术，特别是定向进化的稳定人造细胞的研究。一个“自下而上”的程序来创造人造细胞，避免了管理现代活细胞的复杂性的需要，而在“自上而下”的方法中，管理是最小化细胞所必需的。然而，反过来，它需要一种比天然细胞的“水-油-水”结构更简单的细胞结构。这项研究的重点是通过控制表面活性剂来控制相分离，从而形成细胞内水外油的细胞结构。表面活性剂是一种小分子，它的一面“倾向于”朝向水，另一面更倾向于朝向油。这些分子决定了水和油之间的边界和界面的性质，反过来又可以用于大小均匀的人工细胞的可再生制备。20年来，人们一直在寻找这种控制方法，而“现成的”表面活性剂使这种控制成为可能，这将推动使用自下而上的方法制造人造细胞的努力。这项研究的重点是将遗传系统整合到人工细胞中，这些遗传系统本身可以进化，最终以一种改变细胞适应性的方式影响细胞的特性。该项目将创建合成管道来制造表面活性剂，这种表面活性剂可以对水-油乳剂的物理性质进行可重复性控制，从而制备出稳定、坚固且尺寸均匀的油纳米液滴（合成细胞）。我们将开发不会使细胞内的酶、基因和其他生物变性的表面活性剂。人工细胞结构只涉及两个相，即外部脂质相和内部水相。允许向细胞输送水和其他小分子的系统将被整合到合成细胞中。这项研究的目标是创造一种机制，通过这种机制，合成细胞可以根据细胞内发生的分子进化过程改变其外部特征。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。

With this award, the Chemistry of Life Processes (CLP) Program in the Division of Chemistry is funding work under the direction of Dr. Steven Benner from the Foundation for Applied Molecular Evolution to create stable artificial cells that may be used in biotechnology, especially in directed evolution. A "bottom-up" program to create artificial cells avoids the need to manage the complexity of modern living cells, a management necessary in "top-down" approaches to minimal cells. However, it requires in turn a cellular architecture simpler than the "water-oil-water" architecture of natural cells. The research focuses on gaining control over phase separation that creates a cell structure with water inside the cell and oil outside through control over surfactants, which are small molecules that have a side that "prefers" to orient toward water and another side that prefers to orient toward the oil. These molecules determine the properties of boundaries and interfaces between the water and oil and in turn can be used in the reproducible preparation of artificial cells that are uniform in size. Such control has been sought for 20 years now and the availability of "off-the-shelf" surfactants that make control possible would boost the efforts to create an artificial cell using a bottom up approach. The research focuses on the incorporation into the artificial cell of genetic systems that themselves can evolve, ultimately to influence the properties of the cells in a way that alters cellular fitness.This project will create synthetic pipelines to make surfactants that give reproducible control over the physical properties of water-oil emulsions from which stable, robust and uniformly sized nanodroplets (synthetic cells) in oil can be prepared. We will develop surfactants that do not denature the enzymes, genes, and other biologics that reside within the cells. The artificial cell architecture involves just two phases, an external lipid phase and internal water phase. Systems that allow the delivery of water and other small molecules to the cell will be integrated in the synthetic cells. The research will then aim to create a mechanism by which the synthetic cells can change their external traits in response to molecular evolution processes that takes plan in the cell.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.