Transitions: Emergent Microstructures of Protocells

细胞是生物体的基本组成部分，细胞的一个关键特性是它们的自我繁殖能力。该项目的一个目标是通过构建和研究主要包含自我繁殖成分的精简（最小）合成细胞来探索细胞和自我繁殖的起源。项目的其他目标是为PI提供冷冻电子显微镜方面的培训，这将有助于对基于rna的最小合成细胞进行详细分析，建立一个具有此类技术经验的研究项目，并培训学生将来参加美国的劳动力。理解如何构建合成生命是一项基础科学和工程挑战。由于所有已知的生命都被封装在细胞中，并且还需要遗传信息，因此一种非常简单的生命形式可能是被封装在膜泡（原始细胞）中的RNA。通过实验研究原始细胞，对细胞的生物物理和进化重要性有了新的认识。然而，目前对原始细胞的研究受到实验技术的限制，这些实验技术测量的是整体的特性，而不是单个的原始细胞。这个过渡方案的总体目标是通过接受低温电子显微镜（EM）技术的培训和使用，使个体原始细胞和RNA结构的分析成为可能。技术目标将是研究原始细胞内部的微观组织和内容物在后代中的分布。建立冷冻电镜作为一种分析原始细胞的技术，将为这些简单的类生命结构的基础研究打开一扇大门。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。

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.