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

在过去的一个世纪里，对活细胞功能的生物学研究推动了医学、工业的进步，并使我们对生命的理解有所提高。即使有了这些非凡的科学发现，科学家们仍然远远不能理解细胞生命的许多基本原理。合成生物学是一个集分子生物学、生物化学、计算科学和工程学于一体的领域。这项研究的基本原理是充分了解化学成分是如何聚集在一起形成一个活细胞的。这项研究可能导致从非生物部分构建细菌细胞。克雷格·文特尔研究所（J. Craig Venter Institute）最近的研究工作制造出一种细菌细胞，这种细胞只有维持生命所必需的极少一组基因。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种种进步，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。通过这个项目创造的合成细菌细胞将催化生物知识的扩展，这可能会带来更好的健康，改善生物制造，保护环境的新工具，以及其他将改善各地人类生活的应用。待研究的生命法则在分子水平上提出了这样的问题：一个生物体有哪些必要的组成部分才能称得上是活着的？研究人员将利用实验研究的结果来发展理论框架，以理解活细胞的基本组成部分和关键要素。为了制造一个合成细胞，这个项目将结合来自不同领域的三位科学家的专业知识。项目负责人约翰·格拉斯（John Glass）是一名合成生物学家，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。凯特·阿达玛拉是一位生物化学家，擅长制造非活细胞样囊泡。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分。该团队将合成一个能够编程细胞和细胞硬件（如酶、膜、氨基酸、盐和维生素）的合成DNA基因组，从而形成一个细菌细胞。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。

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.