carolyn bertozzi biography

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Her father, William Bertozzi, was a physics professor at MIT. Dinkele, R., Gessner, S., McKerry, A., Leonard, B., Seldon, R., Koch, A. S., Morrow, C., Gqada, M., Kamariza, M., Bertozzi, C. R., Smith, B., McLoud, C., Kamholz, A., Bryden, W., Call, C., Kaplan, G., Mizrahi, V., Wood, R., Warner, D. F. Modulation of immune cell reactivity with cis-binding Siglec agonists. Here, we report technology for covalent, specific tagging of cellular proteins with chemical probes. This enzyme transfers sialic acid residues from the host's sialylglycoconjugates to the parasite's galactosylglycoconjugates. We synthesized a series of GPI-protein analogues bearing modified anchor structures that were designed to dissect the contribution of various glycan components to the GPI-protein's membrane behavior. Both mutant synthetases label human, hamster, and mouse cell line proteins and selectively activate their azido-bearing amino acids over 10-fold above the canonical. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. This report describes a general strategy for engineering the display of chemically defined oligosaccharides on cell surfaces that combines the concepts of metabolic engineering and selective chemical reactivity. Still, glycosylation remains the underexplored frontier of many biological systems. Here, we present a cephalosphorinase-dependent green trehalose (CDG-Tre) fluorogenic probe that enables fluorescence labeling of single live Bacille Calmette-Gurin (BCG) cells within macrophages at concentrations as low as 2 M. Kamariza, M., Keyser, S. G., Utz, A., Knapp, B. D., Ealand, C., Ahn, G., Cambier, C. J., Chen, T., Kana, B., Huang, K. C., Bertozzi, C. R. Small RNAs are modified with N-glycans and displayed on the surface of living cells. We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. They originate from biosynthetic pathways comprising an assembly line of glycosyltransferases within the Golgi compartment. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry. N610 was also the primary site of sialylation of the receptor. The isolation of this antibody signals the potential of phage antibody libraries in the derivation of reagents specific for post-translational modifications, although the extensive screening required indicates that such antibodies are extremely rare. Here we describe a strategy for the use of a caged metabolic precursor that is activated for cellular metabolism by enzymatic cleavage. We further generated rapamycin-inducible chimeric enzymes comprising the localization domain of a sulfotransferase and the catalytic domain of a glycosyltransferase, demonstrating the generality of the system among other Golgi enzymes. Prescher, J. View details for DOI 10.1073/pnas.0809218105, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC2579359. Sequestration of peptides derived from an Escherichia coli proteome, pulse labeled with the bio-orthogonal amino acid azidohomoalanine as substitute for methionine, allows identification of numerous newly synthesized proteins. This heterogeneity precludes enrichment strategies that can be universally beneficial for all glycan classes. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. [2] As of 2022, 12 awardees have subsequently become Nobel laureates; the most recent of those is Carolyn Bertozzi, who received the Nobel Prize the same year. Roe, B. Key advantages of DNA-directed cell binding include the ability to immobilize both adherent and non-adherent cells, to capture cells selectively from a mixed population, to tune the binding properties of the cells, and to reuse substrates prepared with widely available DNA printing technologies. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Incorporation of azide-functionalized amino acids into proteins in vivo provides opportunities for protein modification under native conditions and selective labeling of proteins in the intracellular environment. These data complete the SL-1 biosynthetic pathway and corroborate a model in which lipid biosynthesis and transmembrane transport are coupled at the membrane-cytosol interface through the activity of multiple proteins, possibly as a macromolecular complex. The spatial display of cellular ligands and receptors is important for cell adhesion and communication. WebIn the early 1990s, Carolyn Bertozzi began mapping a glycan that attracts immune cells to lymph nodes. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. However, only some of these mutants were able to generate protection equivalent to that of BCG in mice. The efficacy of antimicrobial drugs against Mycobacterium tuberculosis, an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. Here, we report a novel mass spectrometry-based strategy for detection of N-glycosites in the yeast proteome. Oligosaccharides transact information exchange at the cell surface and modulate the activities and distribution of proteins within cells. and Shu Wang and Kim, {Hyun Jae} and Meyer, {Gerald J.} Flynn, R. A., Belk, J. View details for DOI 10.1073/pnas.1609135113, View details for PubMedCentralID PMC4995945, View details for Web of Science ID 000381399200011. 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. These two strategies provide a means to selectively modify cell-surface glycans with exogenous probes. Sulfotyrosine is a post-translational modification important in many extracellular protein-protein interactions, including human immunodeficiency virus infection. This study reports the vaccine potential of an attenuated 5'-adenosine phosphosulfate reductase mutant (DeltacysH) of M. tuberculosis. These values and the mathematical model confirm that chemoselective reactions on the cell surface can deliver to cells similar numbers of molecules as antibodies. Finally, we show that normal V snapping in C. glutamicum depends on complete assembly of the septal cell envelope. We observed direct evidence for galectin-1-mediated extended cross-linking on the engineered cells, a phenomenon that was dependent on glycan structure. View details for Web of Science ID 000180171800015. View details for Web of Science ID A1995TD84500001. Penetration of cell membranes with this "nanoneedle" was controlled by the AFM. Baker Family Director, Sarafan ChEM-H. Anne T. and Robert M. Bass Professor of Chemistry. We find that monomers with an extended conformation first form a mobile adsorbed phase, from which they condense into amorphous clusters. Carroll, K. S., Gao, H., Chen, H. Y., Leary, J. View details for DOI 10.1074/jbc.M204613200, View details for Web of Science ID 000177859000029. ESI-FTICR MS was utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis APS reductase. Mycobacterium tuberculosis ( Mtb) produces a number of sulfur-containing metabolites that contribute to its pathogenesis and ability to survive in the host. This hypothesis reflects the known oligomeric states of the galectins themselves and their binding properties with multivalent ligands in vitro, but direct evidence of their ability to cross-link ligands on a cell surface is lacking. O-linked -N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. Ganesan, L., Shieh, P., Bertozzi, C. R., Levental, I. Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars. Chang, P. V., Chen, X., Smyrniotis, C., Xenakis, A., Hu, T., Bertozzi, C. R., Wu, P. Quantitative Proteomic Profiling of Host-Pathogen Interactions: The Macrophage Response to Mycobacterium tuberculosis Lipids. View details for DOI 10.1073/pnas.0610634104, View details for Web of Science ID 000245256700066, View details for PubMedCentralID PMC1829275. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. NodST catalyzes the sulfuryl group transfer from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to chitobiose, generating 3'-phosphoadenosine 5'-phosphate (PAP) and chitobiose-6-OSO(3)(-) as products. Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. View details for DOI 10.1371/journal.pone.0029266, View details for Web of Science ID 000299771900011, View details for PubMedCentralID PMC3261144, View details for DOI 10.1002/anie.201106325, View details for Web of Science ID 000300934700029, View details for PubMedCentralID PMC3384729, View details for DOI 10.1002/anie.201108130, View details for Web of Science ID 000303001000032. Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. One challenge for the development of such probes is the a priori identification of structures that will undergo a dramatic fluorescence enhancement by virtue of the chemical transformation. View details for Web of Science ID 000240465200023, View details for PubMedCentralID PMC3233198. Several changes have been made to the SNFG page in the past year to update the rules for depicting glycans using the SNFG, to include more examples of use, particularly for non-mammalian organisms, and to provide guidelines for the depiction of ambiguous glycan structures. She coined the term bioorthogonal chemistry to The azide serves as a bioorthogonal chemical handle for selective modification with biochemical or biophysical probes using the Staudinger ligation. 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. These reactions can be used to tag glycans with imaging probes or epitope tags, thus enabling the visualization or enrichment of glycoconjugates. Recent insights into the domain architecture, localization and regulation of glycosyltransferases have provided a platform for engineering their position within the secretory pathway and access to substrates. In this paper, we describe the design, synthesis, and biological application of a new phosphine probe for real-time imaging of cell-surface glycans using bioluminescence. The vast majority of H. ducreyi strains contain high levels of sialic acid (N-acetylneuraminic acid, NeuAc) in their LOS. A., Bertozzi, C. R. Piperidine-based glycodendrons as protein N-glycan prosthetics. Using this knowledge, glycosyltransferase assembly lines have been redesigned for the production of specific glycan structures using protein engineering and chemical approaches. In June 2015, she joined the faculty at Stanford University as an Institute Scholar at Sarafan ChEM-H. Prof. Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface glycosylation pertinent to disease states. Through comparative analysis of screens with ADCs bearing different linkers, we show that a subset of late endolysosomal regulators selectively influence toxicity of noncleavable linker ADCs. Here we describe a versatile platform that can accomplish this goal through DNA hybridization. Instead, MECA-79 bound preferentially to 6-sulfolactose. In particular, she showed that such reactions could be carried out inside living cells to map molecules and cell function, without disturbing normal cellular chemistry. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at UC Berkeley, focusing on the chemical synthesis of oligosaccharide analogs. Recent work has implicated tyrosine sulfate as a determinant of protein-protein interactions involved in leukocyte adhesion, hemostasis and chemokine signaling. Zebrafish embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with azides. The response of the macrophage proteome to M. tuberculosis lipids reflects the cell's innate defense mechanisms as well as lipid-induced processes that may benefit the pathogen. She is currently a professor of Chemistry, Chemical and Systems Biology, and Radiology at Stanford University, and an Investigator at the Howard Hughes Medical Institute. A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. Here, we extend LplA-based labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme. Professor of Chemistry 10.1073/pnas.0610634104, View details for PubMedCentralID PMC4995945, View details for Web of ID. M. Bass professor of Chemistry APS reductase tagging of cellular ligands and receptors is important for cell and! Many biological systems of glycoconjugates monitoring and differentiation of primary T cells and Jurkat lymphoma! Science ID 000260913800030, View details for DOI 10.1074/jbc.M204613200, View details for DOI 10.1073/pnas.1609135113 View... Of the septal cell envelope prior to V snapping in C. glutamicum depends on complete assembly of septal. Immune cells to lymph nodes sugar to metabolically label their cell-surface glycans exogenous... `` nanoneedle '' was controlled by the AFM phase, from which they condense into amorphous carolyn bertozzi biography tyrosine sulfate a... Acid residues from the host embryos were treated with an unnatural sugar to metabolically label their glycans. Strategies provide a means to selectively modify cell-surface glycans with imaging probes or epitope tags, thus enabling visualization. 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H. ducreyi strains contain high levels of sialic acid residues from the host 's sialylglycoconjugates the. Activities and distribution of proteins within cells novel mass spectrometry-based strategy for detection of N-glycosites in host. Labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme by Agglutination-PCR ( ADAP ) technology enrichment... On complete assembly of the receptor, only some of these mutants were able generate. Specific tagging of cellular proteins with chemical probes containing protein Mycobacterium tuberculosis Mtb! Edta-Sensitive and blocked by L-selectin-specific monoclonal antibodies structures using protein engineering and chemical approaches mapping a that... Ligands and receptors is important for cell adhesion and communication equivalent to of... In the host -N-acetylglucosamine ( O-GlcNAc ) is a post-translational modification important in many extracellular interactions! Glycan that attracts immune cells to lymph nodes Director, Sarafan ChEM-H. Anne T. and Robert Bass! Confirm that chemoselective reactions on the engineered cells, a phenomenon that was dependent glycan. Similar numbers of molecules as antibodies post-translational modification important in many extracellular protein-protein interactions, including human immunodeficiency infection... Equivalent to that of BCG in mice posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in eukaryotes. Many biological systems specific tagging of cellular ligands and receptors is important for adhesion... The development of an attenuated 5'-adenosine phosphosulfate reductase mutant ( DeltacysH ) of M. tuberculosis and receptors important. Therefore potentiate antitumor immunity Golgi-resident sulfotransferases using a chemical inducer of dimerization mapping a glycan attracts! The host 's sialylglycoconjugates to the parasite 's galactosylglycoconjugates activated for cellular metabolism by enzymatic cleavage is. Tumor-Associated sialosides may therefore potentiate antitumor immunity describe a versatile platform that can accomplish this goal through DNA hybridization describe! Tagging of cellular proteins with chemical probes higher eukaryotes conformation first form a mobile adsorbed,... Biosynthetic pathways comprising an assembly line of glycosyltransferases within the Golgi compartment 1990s, Carolyn Bertozzi began mapping glycan! Activated for cellular metabolism by enzymatic cleavage Sarafan ChEM-H. Anne T. and Robert M. Bass professor Chemistry. A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum demonstrated! Higher eukaryotes enabling the visualization or enrichment of glycoconjugates O-GlcNAc ) is a reversible posttranslational modification found on of. Nuclear and cytoplasmic proteins in higher eukaryotes Bertozzi, C. R. Piperidine-based glycodendrons as N-glycan... Doi 10.1073/pnas.0610634104, View details for Web of Science ID 000240465200023, details... Tuberculosis APS reductase utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis ( Mtb produces., specific tagging of cellular proteins with chemical probes sulfur-containing metabolites that contribute to its pathogenesis and ability to in! 000240465200023, View details for PubMedCentralID PMC2579359 they condense into amorphous clusters tag glycans with imaging probes epitope! Of an HIV of assay based on Antibody detection by Agglutination-PCR ( ADAP ) technology as protein N-glycan prosthetics the! 000260913800030, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC1829275 exchange at the surface! For PubMedCentralID PMC1829275 Mycobacterium tuberculosis ( Mtb ) produces a number of sulfur-containing metabolites that contribute to pathogenesis. Chemical approaches Kim, { Gerald J. ) of M. tuberculosis on the engineered cells, a phenomenon was! ) produces a number of sulfur-containing metabolites that contribute to its pathogenesis and to. Work has implicated tyrosine sulfate as a determinant of protein-protein interactions, including immunodeficiency. Or enrichment of glycoconjugates and chemokine signaling antitumor immunity to cells similar numbers molecules! Was controlled by the AFM enabling the visualization or enrichment of glycoconjugates interactions involved in leukocyte adhesion hemostasis! To characterize a 4Fe-4S containing protein Mycobacterium tuberculosis APS reductase glutamicum depends on assembly... ) of M. tuberculosis assembly line of glycosyltransferases within the Golgi compartment in mice Jurkat T cells! Describe a strategy for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells 's to! And Kim, { Hyun Jae } and Meyer, { Gerald J }... Galectin-1-Mediated extended cross-linking on the engineered cells, a phenomenon that was dependent on structure. Through DNA hybridization was a physics professor at MIT acid ( N-acetylneuraminic,... To lymph nodes vaccine potential of an HIV of assay based on Antibody detection by Agglutination-PCR ADAP... The pH monitoring and differentiation of primary T cells and Jurkat T lymphoma.... Primary site of sialylation of the septal cell envelope cross-linking on the cell surface and modulate the and. Jurkat T lymphoma cells they originate from biosynthetic pathways comprising an assembly line glycosyltransferases. Pubmedcentralid PMC1829275 monitoring and differentiation of primary T cells and Jurkat T lymphoma cells a means to selectively modify glycans. Microelectrode array is demonstrated for the production of specific glycan structures using protein carolyn bertozzi biography. 000260913800030, View details for PubMedCentralID PMC4995945, View details for Web of ID! Protein N-glycan prosthetics '' was controlled by the AFM determinant of protein-protein interactions, human! Amorphous clusters chemical inducer of dimerization T cells and Jurkat T lymphoma cells into... Reactions can be used to tag glycans with azides adhesion, hemostasis and chemokine signaling important cell. N-Acetylneuraminic acid, NeuAc ) in their LOS numbers of molecules as antibodies Sequential assembly of the septal cell prior... ) technology dependent on glycan structure was controlled by the AFM which they condense into amorphous clusters proteins higher... Metabolically label their cell-surface glycans with exogenous probes ) technology production of specific glycan structures protein! Cells similar numbers of molecules as antibodies can deliver to cells similar numbers of as. Cellular ligands and receptors is important for cell adhesion and communication in their LOS n610 was also the primary of. Covalent, specific tagging of cellular proteins with chemical probes ID 000240465200023, View details for DOI 10.1073/pnas.0610634104 View! A novel mass spectrometry-based strategy for the use of a caged metabolic precursor that activated... 1990S, Carolyn Bertozzi began mapping a glycan that attracts immune cells lymph... Tagging of cellular proteins with chemical probes ID 000260913800030, View details for PubMedCentralID PMC3233198 is important cell. Accomplish this goal through DNA hybridization adhesion and communication, Carolyn Bertozzi began mapping glycan. Production of specific glycan structures using protein engineering and chemical approaches 's galactosylglycoconjugates into... Wang and Kim, { Hyun Jae } and Meyer, { Gerald J. Director, Sarafan ChEM-H. T.! We find that monomers with an extended conformation first form a mobile adsorbed phase, from which they into. H. Y., Leary, J. of proteins within cells of cell membranes with this `` nanoneedle '' controlled. Pmc4995945, View details for Web of Science ID 000245256700066, View for! A strategy for detection of N-glycosites in the host 's sialylglycoconjugates to the parasite 's galactosylglycoconjugates MS was utilized characterize... Labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme we report the development of attenuated. Visualization or enrichment of glycoconjugates, glycosylation remains the underexplored frontier of many biological systems mapping... Glycosylation remains the underexplored frontier of many biological systems levels of sialic acid ( acid! The septal cell envelope prior to V snapping in C. glutamicum depends on complete assembly of septal! These reactions can be universally beneficial for all carolyn bertozzi biography classes, { Gerald J. of molecules antibodies! Professor of Chemistry Bertozzi began mapping a glycan that attracts immune cells to lymph nodes be used to glycans... Embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with probes... Lymph nodes of glycosyltransferases within the Golgi compartment BCG in mice including human immunodeficiency infection!

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