Metabolic Engineering with Bioorthogonal Chemical Reporters

点击翻译按钮获取中文摘要

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.