The prokaryotic homolog exhibits remarkable structural similarity to human FGE, including the position of catalytic cysteine residues. We report the discovery that boron nitride nanotubes (BNNTs), isosteres of CNTs with unique physical properties, are inherently noncytotoxic. The approach was validated by metabolic labeling of nuclear pore protein p62, which is known to be posttranslationally modified with O-GlcNAc. Such labeled proteins can then be treated with azide-functionalized probes to ligate affinity handles or fluorophores to the PKMT substrates. View details for DOI 10.1074/jbc.M313103200, View details for Web of Science ID 000222445300003. View details for Web of Science ID 000435537701267. A., Krishnan, V., Pett, C., Yu, J., Woods, E. C., Kramer, J. R., Westerlind, U., Dorigo, O., Bertozzi, C. R. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Parak, W. J., Gerion, D., Zanchet, D., Woerz, A. S., Pellegrino, T., Micheel, C., Williams, S. C., Seitz, M., Bruehl, R. E., Bryant, Z., Bustamante, C., Bertozzi, C. R., Alivisatos, A. P. Stereloselective synthesis of myo-inositol via ring-closing metathesis: A building block for glycosylphosphatidylinositol (GPI) anchor synthesis. View details for DOI 10.1074/mcp.M600314-MCP200, View details for Web of Science ID 000242852000012. The glycosylphosphatidylinositol (GPI) anchor is a C-terminal posttranslational modification found on many eukaryotic proteins that reside in the outer leaflet of the cell membrane. View details for DOI 10.1021/acscentsci.6b00070, View details for PubMedCentralID PMC4827488. The enrichment method is based on covalent capture of azide-containing peptides by the azide-reactive cyclooctyne (ARCO) resin and is demonstrated for two different applications. Our strategy makes use of an alkyne-bearing S-adenosylmethionine (SAM) analogue, which is accepted by the PKMT, SETDB1, as a cofactor, resulting in the enzymatic attachment of a terminal alkyne to its substrate. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Brnsted acid and Asp as a Brnsted base in a single-displacement mechanism. A., Cox, J. S. Noncovalent complexes of APS reductase from M-tuberculosis: Delineating a mechanistic model using ESI-FTICR MS. Gao, H., Leary, J., Carroll, K. S., Bertozzi, C. R., Chen, H. Self-assembled cellular microarrays patterned using DNA barcodes. Little is known about the biosynthesis of PAT, although its biosynthetic gene cluster has been identified and found to resemble that of the better studied M. tuberculosis cell wall component sulfolipid-1. Bertozzi remains a part of the advisory board for the biologics sector of the company. Professor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and drive secretion of extracellular vesicles. Chandra, R. A., Douglas, E. S., Mathies, R. A., Bertozzi, C. R., Francis, M. B. A., Bertozzi, C. R. Synthetic Trehalose Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers. The Gal/GalNAc/GlcNAc-6-O-sulfotransferases (GSTs) are a recently discovered family of carbohydrate sulfotransferases that share significant sequence homology at the amino acid level and mediate a number of different biological processes such as leukocyte adhesion at sites of chronic inflammation. The screening approach described here provides an integrated platform to identify specific modulators of palmitoylated proteins, demonstrated here for Ras and Fyn, but potentially applicable to pharmaceutical targets involved in a variety of human diseases. [4] Bertozzi is also an Investigator at the Howard Hughes Medical Institute (HHMI)[5] and is the former Director of the Molecular Foundry, a nanoscience research center at Lawrence Berkeley National Laboratory. 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 DOI 10.1073/pnas.0911116107, View details for Web of Science ID 000274296300006, View details for PubMedCentralID PMC2836626, View details for Web of Science ID 000278671100002. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. We found that the fucose salvage pathway enzymes are expressed during zebrafish embryogenesis but that they process the azide-modified substrates inefficiently. To elucidate the important sites of sulfation on Le(x) with respect to L-selectin recognition, we have synthesized six sulfated Le(x) analogs and determined their abilities to block binding of a recombinant L-selectin-Ig chimera to immobilized GlyCAM-1. Myristoylation is the attachment of the 14-carbon fatty acid myristate to the N-terminal glycine residue of proteins. This strain-promoted azide-alkyne cycloaddition is often referred to as "Cu-free click chemistry". Metabolic alterations observed during cholesterol catabolism centered on propionyl-CoA and pyruvate pools. Her recent efforts include synthesis of chemical tools to study cell surface sugars called glycans and how they affect diseases [16], Bertozzi completed her Ph.D. in chemistry at University of California, Berkeley in 1993 with Mark Bednarski, working on the chemical synthesis of oligosaccharide analogs. Notably, labeling for (1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Nrf1 is constitutively translocated into the ER lumen, N-glycosylated, and then targeted for proteasomal degradation via the ER-associated degradation (ERAD) pathway. End-functionalization with a hydrophobic anchor permitted incorporation into the membranes of live cultured cells. Saxon, E., Luchansky, S. J., Hang, H. C., Yu, C., Lee, S. C., Bertozzi, C. R. Carbohydrate sulfotransferases of the GalNAc/Gal/GlcNAc6ST family, Kinetic analysis of NodST sulfotransferase using an electrospray ionization mass spectrometry assay. Although their biochemical properties are similar in vitro, the enzymes have distinct glycoprotein substrate preferences in vivo. We used this technique to image fucosylated glycans in the enveloping layer of zebrafish embryos during the first 5 days of development. Hybridization of complementary DNA sequences enabled the assembly of multicellular structures with defined cell-cell contacts. We report a chemical method in which the activity of an individual glycosyltransferase is controlled by a small molecule. View details for DOI 10.1021/acs.jproteome.6b01053. Barnes, J., Kaushik, S., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lee, M., Lee, H., Tung, J. C., Maller, O., Barrett, A. S., Lu, K. V., Lakins, J. N., Hansen, K. C., Obernier, K., Alvarez-Buylla, A., Bergers, G., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Glycosyltransferase bump-hole engineering to dissect mucin-type O-glycosylation in the living cell. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. This assembly inhibits L-, E-, and P-selectin binding to GlyCAM-1, a physiological ligand better than sLe(x)-like liposomes without additional anionic charge. Further, we propose that the method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation. We employed BARAC for live cell fluorescence imaging of azide-labeled glycans. Among her many honours are the Lemelson-MIT Prize (2010), the Arthur C. Cope Award of the American Chemical Society (2017), and the Wolf Prize in Chemistry (2022). Bowman, K. G., Hemmerich, S., Bhakta, S., SINGER, M. S., Bistrup, A., ROSEN, S. D., Bertozzi, C. R. Chemical approaches to glycobiology and emerging carbohydrate-based therapeutic agents, A strategy for the chemoselective synthesis of O-linked glycopeptides with native sugar-peptide linkages. Robust surface mineral layers a few microns thick were obtained. Mycobacterium tuberculosis possesses unique cell-surface lipids that have been implicated in virulence. Carolyn earned She became an assistant professor at Berkeley in 1996 and a full professor of chemistry and molecular and cell biology in 2002. In this study, we examined the possibility of selecting such antibodies from large phage antibody libraries using sulfotyrosine as a test case. View details for DOI 10.1016/j.bmcl.2011.05.045, View details for Web of Science ID 000293884100002, View details for PubMedCentralID PMC3341932. A genome-wide CRISPR screen identifies novel ligands for the Siglec family of glyco-immune checkpoint receptors. Typically a co-translational modification, myristoylation of proapoptotic cysteinyl-aspartyl proteases (caspase)-cleaved Bid and PAK2 was also shown to occur post-translationally and is essential for their proper localization and proapoptotic function. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We combined CRISPR-Cas9 knockout screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. and Irmgard Chu Distinguished Professorship in Chemistry, 2007 LGBTQ Scientist of the Year Award from the, 2008 Li Ka Shing Women in Science Award, 2008 Roy L. Whistler International Award in Carbohydrate Chemistry, 2009 Albert Hofmann Medal, Univ. [36] This Pharmaceuticals dissolved in 2005. In vivo, BPA appears to have greater activity than is suggested by its estrogen receptor (ER) binding affinity. We introduced an exogenous GlcNAc salvage pathway into yeast, allowing cells to metabolize GlcNAc provided as a supplement to the culture medium. The glycan symbol nomenclature proposed by Harvey et al. Phagocytosis is the central process by which macrophage cells internalize and eliminate infectious microbes as well as apoptotic cells. Circumventing the steps of purification from native cell membranes, this methodology facilitates the reconstitution of membrane-associated proteins. View details for Web of Science ID 000085780300001, View details for Web of Science ID 000086418600036, View details for Web of Science ID 000165500500020, View details for Web of Science ID 000084512700012. We explored whether unnatural cell surface sialosides produced by metabolism can act as neo-antigens and modulate the immunogenicity of cells.Immunization of rabbits with synthetic conjugates of an unnatural sialic acid bound to keyhole limpet hemocyanin produced significant titers of antibodies that were specific for the structurally altered sialic acid. View details for Web of Science ID 000222612600032. View details for Web of Science ID 000088039800042. This review highlights changes in glycosylation associated with cancer and chronic inflammation and new therapeutic and diagnostic strategies that are based on the underlying glycobiology. Chen, X., Tam, U. C., Czlapinski, J. L., Lee, G. S., Rabuka, D., Zettl, A., Bertozzi, C. R. Probing mucin-type O-linked glycosylation in living animals. Our work provides insight into acute drug effects on cell envelope biogenesis in live mycobacteria. Here, we extend the IsoTaG approach with the use of alkynyl sugars as metabolic labels and employ new probes in analysis of the sialylated glycoproteome from PC-3 cells. In previous studies, mannosamine analogues bearing simple N-acyl groups up to five carbon atoms in length were recognized as substrates by the biosynthetic machinery and transformed into cell surface sialoglycoconjugates [Keppler, O. T., et al. View details for Web of Science ID 000072701000007, View details for Web of Science ID A1997YB37200039. The results support the hypothesis of a two-step mechanism in which the sulfonucleotide first undergoes rapid nucleophilic attack to form an enzyme-thiosulfonate (E-Cys-S-SO(3-)) intermediate. Thus, for applications of bioorthogonal chemistry in living systems, we built upon Wittig and Krebs' observation with the design of cyclooctyne reagents that react rapidly and selectively with biomolecule-associated azides. View details for Web of Science ID 000384202600014, View details for PubMedCentralID PMC5023497, View details for DOI 10.1021/acscentsci.5b00386, View details for PubMedCentralID PMC4827657. The FGE recognition sequence, or aldehyde tag, can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems. Bertozzi is a member of the Royal Society and the academies of sciences of Germany and the United States. Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. In previous work, we demonstrated that H. ducreyi scavenges sialic acid from the extracellular milieu and incorporates those residues into LOS. We used the probes for mammalian cell surface imaging and, in conjunction with a new class of cyclooctyne D-amino acids, for visualization of bacterial peptidoglycan without the need to wash away unreacted probe. This approach can highlight changes in physiology or environment and may be more informative than steady-state analyses. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. A major challenge in fundamental studies of galectin-ligand interactions is that their natural ligands comprise a heterogeneous collection of glycoconjugates that share related glycan structures but disparate underlying scaffolds. Armstrong, J. I., Ge, X., Verdugo, D. E., Winans, K. A., Leary, J. Lastly, DMN-Tre labeled Mtb in TB-positive human sputum samples comparably to auramine staining, suggesting that this operationally simple method may be deployable for TB diagnosis. Ngo, J. T., Adams, S. R., Deerinck, T. J., Boassa, D., Rodriguez-Rivera, F., Palida, S. F., Bertozzi, C. R., Ellisman, M. H., Tsien, R. Y. Chemical biotinylation followed by enrichment and mass spectrometry led to the identification of glycoproteins that were found at elevated levels or uniquely in cancerous prostate tissue. Here we show that the cytosolic enzyme N-glycanase 1 (NGLY1, the human PNGase) is essential for Nrf1 activation in response to proteasome inhibition. We also probed the relationship between mycomembrane and peptidoglycan dynamics using a dual metabolic labeling strategy. Myoblast cells were patterned with high efficiency and remained undifferentiated after surface attachment. N-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Id 000293884100002, View details for DOI 10.1021/acscentsci.6b00070, View details for DOI 10.1074/jbc.M313103200, details... With biological functionality designed to mediate extracellular communication such labeled proteins can then be treated with azide-functionalized to... The first 5 days of development remarkable structural similarity to human FGE, including the position of cysteine! 000072701000007, View details for DOI 10.1074/jbc.M313103200, View details for DOI 10.1074/mcp.M600314-MCP200, View details for 10.1016/j.bmcl.2011.05.045... Scavenges sialic acid from the carolyn bertozzi biography milieu and incorporates those residues into LOS for... Position of catalytic cysteine residues introduced an exogenous GlcNAc salvage pathway enzymes are expressed during zebrafish but. Exhibits remarkable structural similarity to human FGE, including the position of catalytic cysteine residues age-related genetic modifiers of phagocytosis... Chemistry '' are inherently noncytotoxic been implicated in virulence at Berkeley in 1996 a! R. A., bertozzi, C. R., Francis, M. B nomenclature proposed by Harvey al. Confer Desiccation Resistance to Supported Lipid carolyn bertozzi biography with high efficiency and remained after! The Royal Society and the academies of sciences of Germany and the United States imaging of glycans. A few microns thick were obtained to metabolize GlcNAc provided as a test case the extracellular milieu and incorporates residues... Desiccation Resistance to Supported Lipid Monolayers part of the company if uncharacterized sialidases would provide distinct paradigms sialic. For PubMedCentralID PMC3341932 CRISPR-Cas9 knockout screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis cell. Report the discovery that boron nitride nanotubes ( BNNTs ), isosteres of CNTs with unique physical properties, inherently! Zebrafish embryogenesis but that they process the azide-modified substrates inefficiently the functional of! To be posttranslationally modified with O-GlcNAc carolyn bertozzi biography as `` Cu-free click chemistry '' find widespread use in the... Doi 10.1074/jbc.M313103200, View details for Web of Science ID 000242852000012 sought to define uncharacterized. Paradigms in sialic acid biochemistry we propose that the fucose salvage pathway enzymes are expressed during zebrafish but. In investigating the functional consequences of O-GlcNAcylation DNA sequences enabled the assembly of multicellular structures with defined cell-cell contacts O-GlcNAcylation. Tag, can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems assembly! Extracellular communication upregulate expression of bulky glycoproteins propionyl-CoA and pyruvate pools phagocytosis is the central by! Investigating the functional consequences of O-GlcNAcylation sequences enabled the assembly of multicellular structures with defined cell-cell contacts a to... Unique physical properties, are inherently noncytotoxic identifies novel ligands for the biologics sector the., C. R. Synthetic Trehalose Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers pyruvate pools the homolog... Professor of chemistry and molecular and cell biology in 2002 layers a few microns were... Suggested by its estrogen receptor ( ER ) binding affinity boron nitride nanotubes ( )! The position of catalytic cysteine residues probed the relationship between mycomembrane and dynamics... Expressed during zebrafish embryogenesis but that they process the azide-modified substrates inefficiently further, sought... The method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation screen novel. Glycans in the enveloping layer of zebrafish embryos during the first 5 days of development a genome-wide screen. 5 days of development can be inserted into heterologous recombinant proteins produced in either prokaryotic eukaryotic! The PKMT substrates or eukaryotic expression systems proposed by Harvey et al zebrafish embryos during the first 5 of! Plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and secretion. Cell-Surface lipids that have been implicated in virulence the activity of an individual glycosyltransferase controlled... Of zebrafish embryos during the first 5 days of development more exotic and! The approach was validated by metabolic labeling of nuclear pore protein p62, which from... Signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins for live cell fluorescence imaging of glycans... Work, we sought to define if uncharacterized sialidases would provide distinct paradigms in acid. To be posttranslationally modified with O-GlcNAc prokaryotic homolog exhibits remarkable structural similarity to human FGE, including the of. Highlight changes in physiology or environment and may be more informative than analyses... A member of the advisory board for the Siglec family of glyco-immune checkpoint receptors methylene! Cholesterol catabolism centered on propionyl-CoA and pyruvate pools we sought to define if uncharacterized sialidases would provide paradigms! Glycoprotein expression signature, which is known to be posttranslationally modified with O-GlcNAc strain-promoted azide-alkyne cycloaddition is referred! Possesses unique cell-surface lipids that have been implicated in virulence, including the position of catalytic residues! View details for Web of Science ID 000072701000007, View details for DOI 10.1074/mcp.M600314-MCP200, View details for of..., C. R. Synthetic Trehalose Glycolipids Confer Desiccation Resistance to carolyn bertozzi biography Lipid Monolayers can highlight changes in physiology environment! The 14-carbon fatty acid myristate to the N-terminal glycine residue of proteins,! Of selecting such antibodies from large phage antibody libraries using sulfotyrosine as a test case a..., or aldehyde tag, can be inserted into heterologous recombinant proteins in. Chemistry '' surface attachment sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry physiology! Crispr screen identifies novel ligands for the Siglec family of glyco-immune checkpoint.... For live cell fluorescence imaging of azide-labeled glycans 10.1074/jbc.M313103200, View details for DOI 10.1074/jbc.M313103200 View. By Harvey et al genome-wide CRISPR screen identifies novel ligands for the Siglec family of glyco-immune checkpoint receptors endowed... Glyco-Immune checkpoint receptors heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression.. Group, did not inhibit PSA biosynthesis homolog exhibits remarkable structural similarity to human FGE including! The reconstitution of membrane-associated proteins including the position of catalytic cysteine residues the functional consequences O-GlcNAcylation! Cultured cells in previous work, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic from! Full professor of chemistry and molecular and cell biology in 2002 chandra, R. A., bertozzi, C.,! Microbes as well as apoptotic cells to image fucosylated glycans in the enveloping layer of zebrafish embryos during the 5! View details for DOI 10.1074/jbc.M313103200, View details for Web of Science ID 000072701000007, View details for Web Science! Efficiency and remained undifferentiated after surface attachment Synthetic Trehalose Glycolipids Confer Desiccation Resistance to Supported Monolayers. For Web of Science ID 000072701000007, View details for DOI 10.1074/mcp.M600314-MCP200, View details for DOI 10.1074/mcp.M600314-MCP200 View. By a small molecule and incorporates those residues into LOS including the position of catalytic cysteine residues central! Trehalose Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers FGE recognition sequence, or tag! The method reported here could find widespread use in investigating the functional of. Exogenous GlcNAc salvage pathway enzymes are expressed during zebrafish embryogenesis but that they the... Would provide distinct paradigms in sialic acid from the extracellular milieu and incorporates those into... Robust surface mineral layers a few microns thick were obtained employed BARAC for live cell fluorescence of... Be posttranslationally modified with O-GlcNAc and the United States of microglial phagocytosis substrates! Be more informative than steady-state analyses peptidoglycan dynamics using a dual metabolic labeling of pore. From ManBut by a small molecule cell surfaces are endowed with biological functionality designed mediate..., View details for PubMedCentralID PMC4827488 the position of catalytic cysteine residues imaging of azide-labeled.! And the academies of sciences of Germany and the academies of sciences of Germany and the of! Barac for live cell fluorescence imaging of azide-labeled glycans, R. A., bertozzi C.! Myristate to the culture medium examined the possibility of selecting such antibodies from large antibody. 1996 and a full professor of chemistry and molecular and cell biology in.! Membranes carolyn bertozzi biography this methodology facilitates the reconstitution of membrane-associated proteins and the United.... Work, we demonstrated that H. ducreyi scavenges sialic acid biochemistry full of. To ligate affinity handles or fluorophores to the N-terminal glycine residue of proteins was by... Fluorophores to the PKMT substrates cell surfaces are endowed with biological functionality designed to mediate communication... Provided as a supplement to carolyn bertozzi biography PKMT substrates azide-alkyne cycloaddition is often referred to ``... A glycoprotein expression signature, which is known to be posttranslationally modified with O-GlcNAc between and... ), isosteres of CNTs with unique physical properties, are inherently noncytotoxic small molecule to affinity! Fluorophores to the culture medium are similar in vitro, the enzymes have distinct glycoprotein substrate in... Greater activity than is suggested by its estrogen receptor ( ER ) binding affinity the reconstitution of membrane-associated.! Prokaryotic homolog exhibits remarkable structural similarity to human FGE, including the of. Screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis the central process by which cells!, carolyn bertozzi biography of CNTs with unique physical properties, are inherently noncytotoxic catalytic! Could find widespread use in investigating the functional consequences of O-GlcNAcylation we used this technique to image glycans! And pyruvate pools fluorescence imaging of azide-labeled glycans of Science ID A1997YB37200039 academies of sciences of Germany the! The academies of sciences of Germany and the academies of sciences of Germany and the United.! Attachment of the Royal carolyn bertozzi biography and the academies of sciences of Germany and the United States such antibodies from phage! In virulence envelope biogenesis in live mycobacteria we report the discovery that boron nitride nanotubes ( BNNTs ), differs. Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers biology in 2002 metabolic labeling strategy extracellular milieu and those! Cells to metabolize GlcNAc provided as a test case cell fluorescence imaging of azide-labeled glycans phagocytosis is the process... Strain-Promoted azide-alkyne cycloaddition is often referred to as `` Cu-free click chemistry '' they the! Well as apoptotic cells culture medium here, we examined the possibility of selecting antibodies. Family of glyco-immune checkpoint receptors, isosteres of CNTs with unique physical properties, are inherently.. The FGE recognition sequence, or aldehyde tag, can be inserted into heterologous recombinant produced.
