Imaging macromolecular machines in gene regulation

基因调控中的大分子机器成像

• 批准号: 10254310
• 负责人: David W Taylor
• 金额: $ 38.22万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-05 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10254310
• 关键词: Architecture; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Cryoelectron Microscopy; Disease; Foundations; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Genome engineering; Image; Label; Laboratories; Learning; Link; Macromolecular Complexes; Molecular; Molecular Conformation; Negative Staining; Production; Proteins; Research Personnel; Site; Structure; Translational Research; Work; combat; genome editing; insight; interest; protein function; structural biology; tool

My laboratory is interested in understanding the regulation of gene expression at the molecular level. Our primary tool is cryo-electron microscopy (cryo-EM). We use cryo-EM to study the atomic details of snapshots of our macromolecular machines of interest in action. We have revealed exciting insights into the structure and function of macromolecular machines and assemblies involved in (1) protein production and (2) genome editing. We will continue to apply cryo-EM as well as other tools in our repertoire, including site-specific labeling and conformational analysis using negative stain EM, to produce mechanistic insights into the structure and function of macromolecular machines involved in gene regulation, broadly-defined. In the next five years, my lab plans on elucidating the molecular architectures that set the foundation for accurate gene expression and production of proteins, the workforce of the cell. Combined with the work on CRISPR genome-engineering complexes, these results will have major implications for researchers performing translational research to combat a myriad of diseases.

我的实验室有兴趣了解基因表达在分子水平上的调节， 水平我们的主要工具是冷冻电子显微镜（cryo-EM）。我们用低温电镜研究原子 我们感兴趣的大分子机器的快照的细节。我所降示 对高分子机器和组件的结构和功能的令人兴奋的见解 参与（1）蛋白质生产和（2）基因组编辑。我们将继续应用cryo-EM， 以及其他工具，包括位点特异性标记和构象 使用负染色EM进行分析，以产生对结构和功能的机械见解 基因调控中的大分子机器，广义上来说。在接下来的五年里， 我的实验室计划阐明为精确基因测序奠定基础的分子结构， 蛋白质的表达和生产，细胞的劳动力。结合关于 CRISPR基因组工程复合物，这些结果将对 研究人员进行转化研究，以打击无数的疾病。