Collaborative Research: ProteoCell: The Fat-Free Cell

合作研究：ProteoCell：无脂肪细胞

• 批准号: 1935047
• 负责人: Cheryl Kerfeld
• 金额: $ 71.27万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935047&HistoricalAwards=false
• 关键词: Collaborative; Research; ProteoCell; Fat; Free

This project seeks to build functional, lipid-free, 'living' cells by using proteins to create multi-compartment 'ProteoCells' that can self-generate, house reactions to produce products, interact with other ProteoCells, and in total, define a new type of cell-like structure with fundamentally novel properties. Cells are the most basic unit defining living systems, yet despite years of study, it remains unclear why nature chose to use lipids as its hallmark compartment-formers, and how compartmentalization enables a complex 'soup' of biological molecules to function as an autonomous and self-sustainable unit. This project addresses these questions by using engineering principles to design new protein synthesis reactions, new compartment-forming proteins, and new protein catalysts, and by studying how these 'designer' protein molecules interact with one another to create collective cell-like units. This work will address fundamental Rules of Life questions surrounding the roles of lipids and proteins as essential cellular 'building blocks,' and the importance of compartmentalization in cellular function. Synthetic ProteoCells may ultimately provide an innovative tool to solve societal problems related to human health, sustainability, and the environment. Development of the ProteoCell platform also provides unique educational opportunities and opportunities to engage in a two-way dialog with the public regarding the meaning of a synthetic cell, and the possibilities, benefits, and concerns related to creating new forms of cellular life.Scientifically, this project will define how to 'bottom-up' construct lipid-free ProteoCells, including a self-assembling physical boundary, a genetically programmable cytoplasm, and encapsulated multicomponent reactions. ProteoCells will provide insights into the relationship between the dynamic synthesis of polypeptide/protein building blocks, their self-assembly, and the design rules to create functional ProteoCells that can ultimately self-generate and self-support. The project approach consists of modular and iterative engineering, production, and integration of membrane-forming polypeptides/proteins; protein machinery for CO2 transformation; and machinery to support gene expression. The four aims of the project will create composable ProteoCells and define the range of possible properties; construct rudimentary organelles and define the properties necessary for producing organic molecules from CO2; build multi-cellular ProteoCell 'communities' with defined organization; and probe the US public's perceptions of risks/benefits of constructing a synthetic 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.

该项目旨在通过使用蛋白质创建多室“ProteoCells”来构建功能性、无脂“活”细胞，该细胞可以自我生成、容纳产生产品的反应、与其他ProteoCells相互作用，并总体上定义一种具有根本性新颖特性的新型细胞样结构。细胞是定义生命系统的最基本单位，然而，尽管经过多年的研究，仍然不清楚为什么大自然选择使用脂质作为其标志性的隔室形成者，以及隔室化如何使复杂的生物分子“汤”能够作为一个自主和自我维持的单位发挥作用。该项目通过利用工程原理设计新的蛋白质合成反应、新的隔室形成蛋白质和新的蛋白质催化剂，并通过研究这些“设计”蛋白质分子如何相互作用以创建集体细胞样单位来解决这些问题。这项工作将解决有关脂质和蛋白质作为重要细胞“构建块”的作用以及细胞功能区室化重要性的基本生命规则问题。合成 ProteoCells 最终可能提供一种创新工具来解决与人类健康、可持续发展和环境相关的社会问题。 ProteoCell 平台的开发还提供了独特的教育机会和与公众进行双向对话的机会，涉及合成细胞的含义，以及与创造新的细胞生命形式相关的可能性、好处和关注点。从科学上讲，该项目将定义如何“自下而上”构建无脂 ProteoCells，包括自组装物理边界、基因可编程细胞质和封装的多组分 反应。 ProteoCells 将深入了解多肽/蛋白质构件的动态合成、它们的自组装以及设计规则之间的关系，以创建最终能够自我生成和自我支持的功能性 ProteoCells。该项目方法包括膜形成多肽/蛋白质的模块化和迭代工程、生产和集成；用于二氧化碳转化的蛋白质机器；和支持基因表达的机制。该项目的四个目标将创建可组合的 ProteoCells 并定义可能的属性范围；构建基本细胞器并定义从二氧化碳生产有机分子所需的特性；建立具有明确组织的多细胞 ProteoCell“社区”；并探讨美国公众对构建合成细胞的风险/收益的看法。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。