Administrative Supplement for Equipment Purchase

项目摘要 对新发现的免疫系统的基础研究导致了重要分子工具的发展 用于科学和医学。例如，真核抗体用于诊断和治疗疾病， 原核限制性内切酶用于体外操作DNA序列，原核CRISPR-Cas 适应性免疫系统正在彻底改变基因组编辑、基因治疗和疾病诊断。 最近，已经发现了几种新的免疫系统，其功能仍然未知。的 该提案的重点是确定两个新发现的CRISPR-Cas的结构和功能 适应性免疫系统的主要目标是（i.）填补了我们对这些生物的理解的空白 （ii）提供将这些免疫系统发展成 新的生命科学工具。为了更好地了解这些免疫系统的功能，我们正在使用基于细胞的， 生物化学测定，以及结构方法，如X射线晶体学和cryo-EM。我们希望 确定这些系统如何识别它们的目标，它们如何区分自我和非自我，以及它们如何识别它们的目标。 不同的遗传差异（蛋白质结构域和基因）影响它们的功能。 !

Project Summary Basic research on newly discovered immune systems has led to the development of important molecular tools for use in science and medicine. For example, eukaryotic antibodies are used to diagnose and treat disease, prokaryotic restriction enzymes are used to manipulate DNA sequences in vitro, and prokaryotic CRISPR-Cas adaptive immune systems are revolutionizing genome editing, gene therapy, and disease diagnostics. Recently, several new immune systems have been discovered for which their function remains unknown. The emphasis of this proposal is to determine the structure and function of two newly discovered CRISPR-Cas adaptive immune systems with the primary objectives to (i.) fill gaps in our understanding of these biological systems and (ii) provide the basic mechanistic knowledge necessary to develop these immune systems into new life science tools. To better understand the function of these immune systems we are using cell-based and biochemical assays, as well as structural methods such x-ray crystallography and cryo-EM. We hope to determine how these systems identify their targets, how they distinguish self from non-self, and how their distinct genetic differences (protein domains and genes) impact their function. !