RoL:FELS:RAISE: Building and Modeling Synthetic Bacterial Cells

在过去的世纪里，对活细胞功能的生物学研究导致了医学、工业和我们对生命的理解的进步。即使有了这些非凡的科学发现，科学家们仍然远远没有理解细胞生命的许多最初原理。合成生物学是一个融合了分子生物学、生物化学、计算科学和工程学的领域。这项研究的基本原理是充分了解化学成分如何聚集在一起形成活细胞。这项研究可能会导致从非生命部分构建细菌细胞。克雷格文特尔研究所最近的工作产生了一种细菌细胞，这种细胞只具有生命所必需的最小基因组。这种生物只有474个基因，几乎所有的基因都与地球上其他生物的基因非常相似。尽管生物科学取得了巨大的进步，但研究人员仍然不知道超过三分之一的生命必需基因的功能。通过该项目创建的合成细菌细胞将促进生物学知识的扩展，这可能会导致更好的健康，生物制造的改进，保护环境的新工具以及其他将改善世界各地人类生活的应用。要研究的生命规则在分子水平上要问的是，一个有机体的必要组成部分是什么，才能称之为活的？研究人员将利用实验研究的结果来建立理论框架，以了解活细胞的基本组成和关键元素。为了建立一个合成细胞，这个项目将联合收割机结合三位来自不同领域的科学家的专业知识。该项目的负责人约翰·格拉斯（John Glass）是一位合成生物学家，也是文特尔研究所团队的一员，该团队构建了最小的细菌细胞。Kate Adamala是一位生物化学家，拥有构建非活细胞样囊泡的专业知识。Chris Kempes是一位计算生物学家，他创建了活细胞的数学和计算模型，这些模型将指导选择将要组装的化学部件。该团队将联合收割机合成DNA基因组，能够编程细胞和细胞硬件，如酶，膜，氨基酸，盐和维生素，以这种方式形成细菌细胞。该奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

Over the past century, biological research into how living cells function has led to advances in medicine, industry, and our understanding of what life is. Even with these extraordinary scientific discoveries, scientists still are far from understanding many of the first principals of cellular life. Synthetic Biology is a field that is an amalgam of molecular biology, biochemistry, computational science, and engineering. The rationale for this research is to fully understand how chemical components come together to make a living cell. This research may result in the construction of a bacterial cell from non-living parts. Recent work at the J. Craig Venter Institute produced a bacterial cell that had only a minimal set of genes necessary for life. The organism had only 474 genes and almost all were very similar to genes in the other organisms that live on Earth. Despite all of the advances of biological science, researchers still do not know the function of more than one third of those essential-for-life genes. The synthetic bacterial cells created through this project will catalyze an expansion of biological knowledge that may result in better health, improvements in biomanufacturing, new tools to preserve the environment, and other applications that will enhance the lives of humans everywhere. The rule of life to be investigated asks, on the molecular level, what are the necessary components of an organism that are required to call it alive? The researchers will use results of the experimental studies to develop theoretical frameworks for understanding the basic components and key elements of a living cell.To build a synthetic cell this project will combine the expertise of three scientists from different fields. The project leader, John Glass, is a synthetic biologist and part of the Venter Institute team that constructed the minimal bacterial cell. Kate Adamala is a biochemist with expertise building non-living cell-like vesicles. Chris Kempes is a computational biologist who creates mathematical and computational models of living cells that will guide the selection the chemical parts that will be assembled. This team will combine a synthetic DNA genome capable of programming cell and cellular hardware such as enzymes, membranes, amino acids, salts, and vitamins in such a way as to form a bacterial 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.