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.
The goal of this project is to develop tools from the field of chemistry that can help researchers and. physicians monitor the changes in cell-surface glycans inside the body using imaging techniques. These chemical tools could be useful for cancer detection and diagnosis.
|Jolly, Amber L; Agarwal, Paresh; Metruccio, Matteo M E et al. (2017) Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. FASEB J 31:2393-2404|
|Ganesan, Lakshmi; Shieh, Peyton; Bertozzi, Carolyn R et al. (2017) Click-Chemistry Based High Throughput Screening Platform for Modulators of Ras Palmitoylation. Sci Rep 7:41147|
|Rodriguez-Rivera, Frances P; Zhou, Xiaoxue; Theriot, Julie A et al. (2017) Visualization of mycobacterial membrane dynamics in live cells. J Am Chem Soc 139:3488-3495|
|Zhu, Xuejun; Shieh, Peyton; Su, Michael et al. (2016) A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool. Chem Commun (Camb) 52:11239-42|
|Tsai, Cheng-Ting; Robinson, Peter V; Spencer, Carole A et al. (2016) Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). ACS Cent Sci 2:139-147|
|Lantos, Andrés B; Carlevaro, Giannina; Araoz, Beatriz et al. (2016) Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology. PLoS Pathog 12:e1005559|
|Ngo, John T; Adams, Stephen R; Deerinck, Thomas J et al. (2016) Click-EM for imaging metabolically tagged nonprotein biomolecules. Nat Chem Biol 12:459-65|
|Agarwal, Paresh; Beahm, Brendan J; Shieh, Peyton et al. (2015) Systemic Fluorescence Imaging of Zebrafish Glycans with Bioorthogonal Chemistry. Angew Chem Int Ed Engl 54:11504-10|
|Kim, Justin; Bertozzi, Carolyn R (2015) A Bioorthogonal Reaction of N-Oxide and Boron Reagents. Angew Chem Int Ed Engl 54:15777-81|
|Shieh, Peyton; Dien, Vivian T; Beahm, Brendan J et al. (2015) CalFluors: A Universal Motif for Fluorogenic Azide Probes across the Visible Spectrum. J Am Chem Soc 137:7145-51|
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