Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. We have demonstrated that the quadricyclane ligation is compatible with, and orthogonal to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by performing all three reactions in one pot on differentially functionalized protein substrates. During Bertozzi's third year of graduate school, Bednarski was diagnosed with colon cancer, which resulted in him taking a leave of absence and changing his career path by enrolling in medical school. Hsiao, S. C., Crow, A. K., Lam, W. A., Bertozzi, C. R., Fletcher, D. A., Francis, M. B. Protein glycosylation is a heterogeneous post-translational modification (PTM) that plays an essential role in biological regulation. The findings reported here provide a molecular basis to understand the abnormalities induced in the immune system by the trans-sialidase during T. cruzi infection. Mucin-type O-linked glycoproteins are involved in a variety of biological interactions in higher eukaryotes. View details for Web of Science ID 000304492700020. Wojczyk, B. S., Stwora-Wojczyk, M. M., Hagen, F. K., Striepen, B., Hang, H. C., Bertozzi, C. R., Roos, D. S., Spitalnik, S. L. Metabolic oligosaccharide engineering as a tool for glycobiology, Formation of 1,1-alpha,alpha-glycosidic bonds by intramolecular aglycone delivery. WebBertozzi is trying to drag sugars into the light. Glycosyltransferases responsible for synthesis of cell surface oligosaccharides are therefore essential administrators of cellular communication. The results address the mechanism by which sulfonucleotide reductases protect the covalent but labile enzyme-intermediate before release of sulfite by the protein cofactor thioredoxin. View details for DOI 10.1073/pnas.0506855103, View details for Web of Science ID 000236472500008, View details for PubMedCentralID PMC1405625. Phosphorylation of Rv0516c regulated the abundance of EspA, a virulence-associated substrate of the type VII ESX-1 secretion system. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. [45], In 2019, she co-founded both OliLux Biosciences and Lycia Therapeutics. We demonstrated the noninvasive imaging of glycans in live developing zebrafish, using a chemical reporter strategy. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. In this mechanism, PAPS and trehalose bind and their products are released in random fashion. [24], In 1996 Bertozzi became a faculty member in the UC Berkeley College of Chemistry[25] and a faculty scientist at Lawrence Berkeley National Laboratory, where she served as the Director of the Molecular Foundry. Potential for therapeutics and diagnostics, Kinetic measurements and mechanism determination of Stf0 sulfotransferase using mass spectrometry. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. Binda, O., Boyce, M., Rush, J. S., Palaniappan, K. K., Bertozzi, C. R., Gozani, O. Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation. The vast majority of H. ducreyi strains contain high levels of sialic acid (N-acetylneuraminic acid, NeuAc) in their LOS. Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology. Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19. The first synthesis and characterization of [9]-, [12]-, and [18]cycloparaphenylene was demonstrated utilizing a novel aromatization reaction. The concise synthesis of a coumarin-conjugated cyclooctyne, coumBARAC, that undergoes a 10-fold enhancement in fluorescence quantum yield upon triazole formation with organic azides is reported. The design principles embodied in coumBARAC establish a platform for generating fluorogenic cyclooctynes suited for biological imaging. Sulfation of GlcNAc within sialyl Lewis x is a crucial modification for L-selectin binding, and thus, the underlying sulfotransferase may be a key modulator of lymphocyte trafficking. As sulfated molecules are common mediators of cell-cell interactions, the sulfotransferases and sulfatases may be involved in regulating host-pathogen interactions. These findings suggest a mechanism for the selective uptake of BPA into cells expressing estrone sulfatase. Bertozzi has over 600 publications on Web of Science; the most cited are: Bertozzi grew up in Lexington, Massachusetts, the daughter of the late Norma Gloria (Berringer) and William Bertozzi. Palaniappan, K. K., Pitcher, A. Hatzios, S. K., Baer, C. E., Rustad, T. R., Siegrist, M. S., Pang, J. M., Ortega, C., Alber, T., Grundner, C., Sherman, D. R., Bertozzi, C. R. Imaging the Glycosylation State of Cell Surface Glycoproteins by Two-Photon Fluorescence Lifetime Imaging Microscopy. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Marcaurelle, L. A., Rodriguez, E. C., Bertozzi, C. R. Direct incorporation of unprotected ketone groups into peptides during solid-phase synthesis: Application to the one-step modification of peptides with two different biophysical probes for FRET, Identification of an N-acetylglucosamine-6-O-sulfotransferase activity specific to lymphoid tissue: an enzyme with a possible role in lymphocyte homing. Characterization of the metabolic fates of four TreAz analogues revealed unique labeling routes that can be harnessed for pathway-targeted investigation of the mycobacterial trehalome. The advantage of this ELISA over previous assays is that a macromolecular physiological ligand is employed, rather than a fortuitous or simplified carbohydrate ligand. A., Gray, M. A., Bertozzi, C. R., Rabuka, D., Bassik, M. C. Quantitative super-resolution microscopy of the mammalian glycocalyx. From this global analysis, we have identified a subset of sulfur-metabolizing enzymes that are sensitive to multiple regulatory cues and may be strong candidates for therapeutic intervention. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression. These data are the first to suggest the feasibility of a strategy that improves the efficiency of gene transfer by using the biosynthetic machinery of the cell to engineer novel sugars on the cell surface. They write new content and verify and edit content received from contributors. Mougous, J. D., Petzold, C. J., Senaratne, R. H., Lee, D. H., Akey, D. L., Lin, F. L., Munchel, S. E., Pratt, M. R., Riley, L. W., Leary, J. Genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions observed by ChIRP-MS. Because M. tuberculosis catabolizes host lipids to grow during infection, we propose that growth of M. tuberculosis on fatty acids in vivo leads to increased flux of MMCoA through lipid biosynthetic pathways, resulting in increased virulence lipid synthesis. We observed direct evidence for galectin-1-mediated extended cross-linking on the engineered cells, a phenomenon that was dependent on glycan structure. Delaveris, C. S., Chiu, S. H., Riley, N. M., Bertozzi, C. R. The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans. Furthermore, the method is found to be very specific, as after enrichment over 87% of all peptides contain (modified) azidohomoalanine. View details for DOI 10.1016/j.chembiol.2004.02.023, View details for Web of Science ID 000220502900010. The data from these experiments suggest that the GPI anchor is more than a simple membrane-anchoring device; it also may prevent transient interactions between the attached protein and the underlying lipid bilayer, thereby permitting rapid diffusion in the bilayer. Lim, H. C., Sher, J. W., Rodriguez-Rivera, F. P., Fumeaux, C. n., Bertozzi, C. R., Bernhardt, T. G. The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. [email protected]. Azides installed within cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. Subsequently, the worms were reacted via copper-free click reaction with fluorophore-conjugated difluorinated cyclooctyne (DIFO) reagents. View details for DOI 10.1096/fj.07-9198com, View details for Web of Science ID 000254143700018, View details for PubMedCentralID PMC2865240. Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. Changes in glycosylation are often a hallmark of disease states. de Almeida, G., Sletten, E. M., Nakamura, H., Palaniappan, K. K., Bertozzi, C. R. Synthesis of Heterobifunctional Protein Fusions Using Copper-Free Click Chemistry and the Aldehyde Tag. However, inside infected macrophages, bacteria encounter an environment which differs substantially from broth culture and are subject to important host-dependent pharmacokinetic phenomena which modulate drug activity. Shieh, P., Hangauer, M. J., Bertozzi, C. R. Probing the Mycobacterial Trehalome with Bioorthogonal Chemistry. WebPrincipal Investigator. DMN-Tre labeling was detected within minutes and was inhibited by heat killing of mycobacteria. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate. View details for DOI 10.1021/acs.chemrev.6b00023, View details for Web of Science ID 000389962700001, View details for PubMedCentralID PMC5327817, View details for DOI 10.1021/acscentsci.6b00341, View details for PubMedCentralID PMC5126708. A., Lo, A., Bertozzi, C. R. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Woo, C. M., Felix, A., Byrd, W. E., Zuegel, D. K., Ishihara, M., Azadi, P., Iavarone, A. T., Pitteri, S. J., Bertozzi, C. R. Click-Chemistry Based High Throughput Screening Platform for Modulators of Ras Palmitoylation. However, the copper catalysts are too cytotoxic for long-term exposure with live cells or organisms. Thus, NGLY1 inhibition prevents Nrf1 activation and represents a new therapeutic approach for cancers that depend on proteasome homeostasis. We used these tools to perform the first site-directed mutagenesis study of a member of this sulfotransferase family, GST2. Metabolic labeling can identify recently synthesized glycans and thus directly track glycan dynamics. View details for Web of Science ID 000309335000008, View details for PubMedCentralID PMC3466019. We have coexpressed a human GST-5 cDNA with a GlyCAM-1/IgG fusion protein in COS-7 cells and observed four-fold enhanced [(35)S]sulfate incorporation into this mucin acceptor. Recently, several M. tuberculosis mutants were tested as potential vaccine candidates in the mouse model of tuberculosis. A., Bertozzi, C. R., Marahiel, M. A., Burkart, M. D. Uridine-Based Inhibitors as New Leads for Antibiotics Targeting Escherichia coli LpxC. View details for Web of Science ID 000167162100006, View details for Web of Science ID 000166873000031. Zebrafish embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with azides. These findings extend the known functions of sulfated molecules as general modulators of cell-cell interactions to include those between a bacterium and a human host. Increased sampling sensitivity may allow future TB transmission studies to be extended to sputum-negative and subclinical individuals, and suggests the potential utility of bioaerosol measurement for rapid intervention in other airborne infectious diseases. Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. Bertozzi remains a part of the advisory board for the biologics sector of the company. We show that both Rv1129c and the MCC enzymes are required for intracellular growth in macrophages and that the growth defect of MCC mutants is largely attributable to the degradation of host-derived cholesterol. The structure of CysN*D shows the two proteins in tight association; however, the nucleotides bound to each subunit are spatially segregated. Schump, M. D., Fox, D. M., Bertozzi, C. R., Riley, L. W. Development of IsoTaG, a Chemical Glycoproteomics Technique for Profiling Intact N- and O-Glycopeptides from Whole Cell Proteomes. P., Hangauer, M. J., Bertozzi, C. R. Probing the mycobacterial trehalome with Bioorthogonal Chemistry dmn-tre was... A part of the metabolic fates of four TreAz analogues revealed unique routes! Dependent on glycan structure virulence determinants [ 45 ], in 2019 she. Sulfite by the trans-sialidase during T. cruzi infection be harnessed for pathway-targeted investigation of the GPI anchor have yet be! Cytotoxic for long-term exposure with live cells or organisms OliLux Biosciences and Lycia Therapeutics the glycocalyx successfully the! Polysi exhibited a specific defect in T-cell development because of an inability access! 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