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RoL: RAISE: DESYN-C3: Engineering multi-compartmentalised synthetic minimal cells

RoL：RAISE：DESYN-C3：工程多室合成最小细胞

基本信息

批准号：
1844313
负责人：
Christine Keating
金额：
$ 100万
依托单位：
Pennsylvania State Univ University Park
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 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844313&HistoricalAwards=false
关键词：
RoL RAISE DESYN C3 Engineering

项目摘要

This project aims to create tools for construction of functional artificial cells by building on new insight into how organelles are generated and maintained in natural cells. At a glance, eukaryotic organelles could be described as small intracellular compartments delineated from the rest of the cell content by a membrane made up of molecules called lipids. The organelles are critical for the life of the cell and in turn their formation depends on the self-assembly of the lipids into membranes and on the coexistence of different liquid phases. Consequently the lipid self-assembly and the coexistence of liquid-liquid phases are the object of on-going investigations. In contrast, the interactions between these two processes are largely unexplored. With this award, the Chemistry of Life Processes Program in the Division of Chemistry and the Cellular and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems are funding Dr. Christine Keating from Penn State University and Dr. Kate Adamala from the University of Minnesota to investigate how the two main types of intracellular organizational processes interact with each other. This interdisciplinary research generates a stepping stone on the path to the construction of artificial organelles and in the long term of artificial cells. The research also represents an opportunity for the scientific training and professional development of graduate students, undergraduates, and K-12 teachers. This research project explores cytoplasm-mimicking systems in which lipids and phase-separating proteins are enzymatically produced by cell-free transcription/translation. In vitro lipid biosynthesis pathways are developed for in situ lipid generation in model cytoplasm. The self-assembly of these lipids in the presence of model membraneless organelles is characterized by optical and electron microscopies as well as by permeability measurements. This project seeks to engineer artificial cells capable of producing functional synthetic lipid membranes and inducible stress granules. The findings advance the understanding of physical mechanisms for organellogenesis, and how local lipid production and media compartmentalization impact these mechanisms.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.

该项目旨在通过对细胞器是如何在自然细胞中产生和维持的新见解的基础上，创造用于构建功能性人造细胞的工具。乍一看，真核生物细胞器可以被描述为细胞内的小隔间，由称为脂质的分子组成的膜将其与其余细胞内容物隔开。细胞器对细胞的寿命至关重要，而细胞器的形成又取决于脂类在膜中的自组装以及不同液体的共存。因此，脂类的自组装和液-液两相共存是目前研究的对象。相比之下，这两个过程之间的相互作用在很大程度上是未被探索的。通过这一奖项，化学、生物工程、环境和运输系统部门的生命过程化学计划和化学、生物工程、环境和运输系统部门的细胞和生化工程计划将资助宾夕法尼亚州立大学的Christine Kating博士和明尼苏达大学的Kate Adamala博士研究这两种主要类型的细胞内组织过程如何相互作用。这种跨学科的研究为构建人工细胞器和长期人工细胞提供了一块垫脚石。这项研究也为研究生、本科生和K-12教师的科学培训和专业发展提供了机会。这项研究项目探索了模拟细胞质的系统，在该系统中，类脂和相分离蛋白是通过无细胞转录/翻译来酶促产生的。在体外，脂质生物合成途径被开发用于在模型细胞质中原位生成脂肪。用光学显微镜和电子显微镜以及通透性测量表征了这些脂类在模型无膜细胞器存在下的自组装。该项目致力于设计能够产生功能性合成类脂膜和可诱导应激颗粒的人造细胞。这些发现促进了对器官发生的物理机制的理解，以及当地脂肪生产和媒体划分如何影响这些机制。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。