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

ROL：渴望：DESYN-C3。

• 批准号: 1844290
• 负责人: Steven Benner
• 金额: $ 30万
• 依托单位: Foundation for Applied Molecular Evolution, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844290&HistoricalAwards=false
• 关键词: RoL; EAGER; DESYN; C3.; Bottom

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.

凭借该奖项，化学部的生命过程化学 (CLP) 项目正在资助应用分子进化基金会 Steven Benner 博士指导下的工作，以创建可用于生物技术，特别是定向进化的稳定的人造细胞。创建人造细胞的“自下而上”程序避免了管理现代活细胞的复杂性的需要，而管理是“自上而下”最小细胞方法所必需的。然而，它又需要比天然细胞的“水-油-水”结构更简单的细胞结构。 该研究的重点是获得对相分离的控制，通过控制表面活性剂创建细胞内部有水、外部有油的细胞结构。表面活性剂是小分子，其一侧“倾向于”朝向水，另一侧倾向于朝向油。这些分子决定了水和油之间的边界和界面的特性，进而可用于尺寸均匀的人造细胞的可重复制备。 20年来人们一直在寻求这种控制，而使控制成为可能的“现成”表面活性剂的出现将推动利用自下而上的方法制造人造细胞的努力。 该研究的重点是将自身可以进化的遗传系统融入到人造细胞中，最终以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，对水油乳液的物理特性进行可重复的控制，从而可以在油中制备稳定、坚固且尺寸均匀的纳米液滴（合成细胞）。我们将开发不会使细胞内的酶、基因和其他生物制剂变性的表面活性剂。人造细胞结构仅涉及两个相，外部脂质相和内部水相。允许将水和其他小分子输送到细胞的系统将被集成到合成细胞中。 然后，该研究的目标是创建一种机制，通过该机制，合成细胞可以改变其外部特征，以响应细胞中计划的分子进化过程。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。