Metabolic Engineering with Bioorthogonal Chemical Reporters

生物正交化学报告基因的代谢工程

• 批准号: 9276033
• 负责人: Carolyn Bertozzi
• 金额: $ 49.4万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276033
• 关键词: Anabolism; Animal Model; Azides; Biological; Cancer Detection; Cell surface; Cells; Chemicals; Chemistry; Development; Disease model; Embryonic Development; Engineering; Environment; Eye; Funding; Generations; Global Change; Glycolipids; Goals; Image; Imaging Device; Imaging Techniques; Imaging technology; Instruction; Investigation; Label; Ligation; Malignant Neoplasms; Membrane; Metabolic; Methods; Monitor; Mus; Oligosaccharides; Organism; Pathogenesis; Physicians; Polysaccharides; Reaction; Regulation; Reporter; Research Personnel; Specific qualifier value; System; Techniques; Time; Work; Zebrafish; base; cancer diagnosis; imaging platform; imaging probe; in vivo imaging; metabolic engineering; model building; spatiotemporal; sugar; tool; tumor; tumor progression; zebrafish development

The broad objective of this project is to apply a technique developed in our lab termed metabolic oligosaccharide engineering to in vivo imaging of global changes in the glycome associated with embryonic development and cancer. The "glycome" is the totality of glycans that cells produce under specified conditions of time, space and environment. Changes in the glycome's composition and distribution are associated with embryogenesis and cancer progression. We seek to develop chemical tools for imaging the dynamic cell-surface glycome in living organisms. We plan to pursue five specific aims that further expand the scope of the glycan imaging technology and apply our methods to new avenues of biological investigation. Aim 1 builds directly from our ongoing work in zebrafish imaging, with a shift in focus to disease models in this organism. Aim 2 seeks to expand the glycan imaging technique to bacterial systems, with an eye for monitoring changes in outer membrane glycolipids and capsular polysaccharides that might correlate with pathogenesis. Aim 3 focuses on the , development of probes for imaging glycans in mouse tumor models, building from our earlier work in this model organism. Aim 4 seeks to build the bioorthogonal reaction compendium with second-generation quadricyclane ligation chemistries as well as new reactions based on phosphinoboranes.

这个项目的主要目标是应用我们实验室开发的一种称为代谢的技术。 寡糖工程化以在体内成像与以下相关的糖组中的整体变化 胚胎发育和癌症。“糖组”是细胞在细胞生长条件下产生的聚糖的总和。 特定的时间、空间和环境条件。糖组组成和分布的变化 与胚胎发育和癌症进展有关。我们寻求开发成像的化学工具 生物体中动态的细胞表面糖组。 我们计划追求五个具体目标，进一步扩大聚糖成像技术的范围， 将我们的方法应用于生物学研究的新途径。目标1直接建立在我们正在进行的工作基础上 在斑马鱼成像中，重点转移到这种生物体的疾病模型。目标2旨在扩大 聚糖成像技术用于细菌系统，用于监测外膜的变化 可能与发病机制相关的糖脂和荚膜多糖。目标3侧重于， 在小鼠肿瘤模型中开发用于成像聚糖的探针，基于我们在这方面的早期工作， 模式生物目的4寻求建立第二代生物正交反应体系 四环烷连接化学以及基于膦基硼烷的新反应。