Administrative Supplements to Support Undergraduate Summer Research Experience

支持本科生暑期研究经验的行政补充

• 批准号: 10809490
• 负责人: Ryan Neal Jackson
• 金额: $ 0.92万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10809490
• 关键词: Adaptive Immune System; Administrative Supplement; Antibodies; Basic Science; Biochemical; Biological Assay; Biological Sciences; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Cryoelectron Microscopy; DNA Sequence; Development; Diagnosis; Disease; Genes; Genetic; Immune system; In Vitro; Knowledge; Medicine; Methods; Molecular; Science; Structure; System; Tertiary Protein Structure; Work; X-Ray Crystallography; biological systems; disease diagnostic; experience; gene therapy; genome editing; immune system function; novel; restriction enzyme; summer research; tool; undergraduate student

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. !

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。 !

项目成果

Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA.

• DOI: 10.1038/s41586-022-05559-3
• 发表时间: 2023-01
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Dmytrenko, Oleg;Neumann, Gina C.;Hallmark, Thomson;Keiser, Dylan J.;Crowley, Valerie M.;Vialetto, Elena;Mougiakos, Ioannis;Wandera, Katharina G.;Domgaard, Hannah;Weber, Johannes;Gaudin, Thomas;Metcalf, Josie;Gray, Benjamin N.;Begemann, Matthew B.;Jackson, Ryan N.;Beisel, Chase L.
• 通讯作者: Beisel, Chase L.

Structure of a type IV CRISPR-Cas ribonucleoprotein complex.

• DOI: 10.1016/j.isci.2021.102201
• 发表时间: 2021-03-19
• 期刊: iScience
• 影响因子: 5.8
• 作者: Zhou Y;Bravo JPK;Taylor HN;Steens JA;Jackson RN;Staals RHJ;Taylor DW
• 通讯作者: Taylor DW

Positioning Diverse Type IV Structures and Functions Within Class 1 CRISPR-Cas Systems.

• DOI: 10.3389/fmicb.2021.671522
• 发表时间: 2021
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Taylor HN;Laderman E;Armbrust M;Hallmark T;Keiser D;Bondy-Denomy J;Jackson RN
• 通讯作者: Jackson RN

RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.

• DOI: 10.1038/s41586-022-05560-w
• 发表时间: 2023-01
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Bravo, Jack P. K.;Hallmark, Thomson;Naegle, Bronson;Beisel, Chase L.;Jackson, Ryan N.;Taylor, David W.
• 通讯作者: Taylor, David W.