Transitions: Emergent Microstructures of Protocells

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.