Transitions: Emergent Microstructures of Protocells

细胞是活着的有机体的基本构件，细胞的一个重要属性是它们自我繁殖的能力。这个项目的一个目标是通过建立和研究精简的(最小的)合成细胞来探索细胞和自我繁殖的起源，这些细胞主要包含与自我繁殖有关的成分。其他项目目标是为PI提供冷冻电子显微镜方面的培训，这将促进对基于RNA的最小合成细胞的详细分析，建立一个在此类技术方面有经验的研究计划，并为未来参与美国劳动力培训学生。了解如何构建合成生命是一项基础科学和工程学挑战。由于所有已知的生命都被封装在细胞中，而且还需要遗传信息，所以一种非常简单的生命形式可能是封装在膜泡(原始细胞)中的RNA。对原细胞的实验研究使人们对细胞的生物物理和进化重要性有了新的见解。然而，目前对原始细胞的研究受到实验技术的限制，这些实验技术测量整体的属性，而不是单个的原始细胞。这一过渡计划的总体目标是通过接受培训并使用冷冻电子显微镜(EM)技术来分析单个原细胞及其内部的RNA结构。技术目标将是研究原细胞内的微观组织以及内容物在后代中的分布。建立冷冻-EM作为原始细胞的分析技术，将为这些简单的、类似生命的结构打开基础研究的大门。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。

Cells are the basic building blocks of living organisms, and a crucial property of cells is their ability to self-reproduce. One goal of this project is to explore the origins of cells and self-reproduction by building and studying stripped-down (minimal) synthetic cells that primarily contain components involved in self-reproduction. Additional project goals are to provide the PI with training in cryo-electron microscopy, which will facilitate detailed analyses of RNA-based minimal synthetic cells, to establish a research program that has experience in such techniques, and to train students for future participation in the U.S. workforce.Understanding how to build synthetic life is a fundamental science and engineering challenge. Since all known life is encapsulated in cells and genetic information is also needed, a very simple form of life may be RNA encapsulated inside membrane vesicles (protocells). Studying protocells experimentally yields new insights into the biophysical and evolutionary importance of cells. However, current studies on protocells are limited by experimental techniques that measure properties in bulk, rather than for individual protocells. The overall goal of this Transitions proposal is to enable analyses of individual protocells and the RNA structures within by receiving training for and using the technique of cryo-electron microscopy (EM). The technical goals will be to study the microscopic organization inside protocells and the distribution of contents to successive generations. Establishing cryo-EM as an analytical technique for protocells will open the door to fundamental, previously inaccessible studies of these simple life-like structures.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.