Metabolic Engineering with Bioorthogonal Chemical Reporters

生物正交化学报告基因的代谢工程

• 批准号: 8583049
• 负责人: Carolyn Bertozzi
• 金额: $ 47.64万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 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/8583049
• 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; Life; Ligation; Malignant Neoplasms; Membrane; Metabolic; Methods; Modeling; Monitor; Mus; Oligosaccharides; Organism; Pathogenesis; Physicians; Polysaccharides; Reaction; Regulation; Reporter; Research Personnel; Specific qualifier value; System; Techniques; Time; Work; Zebrafish; base; cancer diagnosis; imaging probe; in vivo imaging; metabolic engineering; 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.

这个项目的总体目标是应用我们实验室开发的一种称为代谢的技术