carolyn bertozzi biography

Professor Carolyn Bertozzi won the 2022 Nobel Prize in Chemistry for a technique she developed to look at tiny strands of sugar on the surface of our cells. In the paper, Dr. Bertozzi and her team described a new method of engineering an antibody to shuttle a targeted extracellular Bouchard, G., Garcia-Marques, F. J., Karacosta, L. G., Zhang, W., Bermudez, A., Riley, N. M., Varma, S., Mehl, L. C., Benson, J. BPA is a substrate for estrogen sulfotransferase, and bisphenol A sulfate (BPAS) and disulfate are substrates for estrone sulfatase. View details for DOI 10.1021/acscentsci.6b00070, View details for PubMedCentralID PMC4827488. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. After completing postdoctoral work at UCSF in the field of cellular immunology, she joined the UC Berkeley faculty in 1996. Here we describe a method for the site-specific introduction of aldehyde groups into recombinant proteins using the 6-amino-acid consensus sequence recognized by the formylglycine-generating enzyme. One of the more remarkable lipids is a sulfated glycolipid, termed sulfolipid-1 (SL-1), which is thought to mediate specific host-pathogen interactions during infection. View details for Web of Science ID 000259675500001, View details for PubMedCentralID PMC2709988. The cell-surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering. Precision glycocalyx editing with antibody-enzyme conjugates is therefore a promising avenue for cancer immune therapy. Lu, C., Jones, T., Pedram, K., Bertozzi, C., Paszek, M., Cui, B. Here, we characterize Mtb's single putative type II sulfatase, Rv3406, as a non-heme iron (II) and -ketoglutarate-dependent dioxygenase that catalyzes the oxidation and subsequent cleavage of alkyl sulfate esters. Wan, S. J., Sullivan, A. Thus, choice of enrichment strategy has profound implications on experimental outcomes. Moreover, the ability of the Rv2131c-encoded enzyme to dephosphorylate PAP and PAPS in vivo was confirmed by functional complementation of an Escherichia coli Delta cysQ mutant. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Using in situ atomic force microscopy to follow 2D assembly of S-layer proteins on supported lipid bilayers, we have obtained a molecular-scale picture of multistage protein crystallization that reveals the importance of conformational transformations in directing the pathway of assembly. However, changes in the glycan structure significantly affected membrane mobility, with the loss of monosaccharide units correlating to decreased diffusion. Malaker, S. A., Pedram, K., Ferracane, M. J., Bensing, B. Sialylated glycans are found at elevated levels in many types of cancer and have been implicated in disease progression. Phagocytosis is the central process by which macrophage cells internalize and eliminate infectious microbes as well as apoptotic cells. Freeman, S. A., Goyette, J., Furuya, W., Woods, E. C., Bertozzi, C. R., Bergmeier, W., Hinz, B., van der Merwe, P. A., Das, R., Grinstein, S. Isotope Targeted Glycoproteomics (IsoTaG) to Characterize Intact, Metabolically Labeled Glycopeptides from Complex Proteomes. 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. Mucin-type O-linked glycoproteins are involved in a variety of biological interactions in higher eukaryotes. Bowman, K. G., Cook, B. N., de Graffenried, C. L., Bertozzi, C. R. The evolving academic research environment, Chemical synthesis of lymphotactin: A glycosylated chemokine with a C-terminal mucin-like domain. Thus, despite its inherent advantages in sample collection, OF is not widely used for population screening. In the 1990s, Dr. Bertozzi was studying glycans, carbohydrates that sit on the surfaces of proteins and cells, the functions of which were not wholly understood. Irradiation of cells with UV light activated the crosslinker, resulting in formation of covalent bonds between O-GlcNAc-modified proteins and neighboring molecules, which could be identified by mass spectrometry. New developments have allowed researchers to begin probing the inner workings of the cell to gain new insight into cell function and metabolism. 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. Cell surface carbohydrates mediate interactions between the cell and its environment. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. CDG-Tre showed high selectivity for mycobacteria over other clinically prevalent species in the Corynebacterineae suborder. Sialic acid is a component of many tumor-associated oligosaccharide antigens. The structure of CysN*D shows the two proteins in tight association; however, the nucleotides bound to each subunit are spatially segregated. [85] Her father was of Italian descent. The importance of nonclassical, multistage crystallization pathways is increasingly evident from theoretical studies on colloidal systems and experimental investigations of proteins and biomineral phases. View details for DOI 10.1073/pnas.0700567104, View details for Web of Science ID 000246599900007, View details for PubMedCentralID PMC1895932. View details for DOI 10.1073/pnas.1012864107, View details for Web of Science ID 000285521500020, View details for PubMedCentralID PMC3003011. Baskin, J. M., Dehnert, K. W., Laughlin, S. T., Amacher, S. L., Bertozzi, C. R. Rapid and selective detection of fatty acylated proteins using omega-alkynyl-fatty acids and click chemistry. Strikingly, this protection from dehydration extends to TDM-phospholipid mixtures with as little as 25 mol % TDM. Electron-based dissociation methods are necessary to capture the O-glycopeptide diversity present in OpeRATOR digestions. Here, we show that Cu(I)-FGE is functional in O2 activation and reveal a high-resolution X-ray crystal structure of FGE in complex with its catalytic copper cofactor. Monomeric and multivalent oligosaccharides that bind to bacterial and viral receptors have been shown to abrogate infection by agents such as Helicobacter pilori, influenza virus and HIV. A broader theme that emerged was the urgent need to bring the glycosciences back into the mainstream of biology by integrating relevant education into the curricula of medical, graduate, and postgraduate training programs, thus generating a critical sustainable workforce that can advance the much-needed translation of glycosciences into a more complete understanding of biology and the enhanced practice of medicine. This review highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems. N-Acetylmannosamine (ManNAc) is the first committed intermediate in the sialic acid biosynthetic pathway; thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. This provides orthogonal cleavage relative to canonical proteases (e.g., trypsin) for improved O-glycopeptide characterization with tandem mass spectrometry (MS/MS). We functionalized cells with short oligonucleotides to impart specific adhesive properties. The assay is based on the release of tritiated formaldehyde from UDP-galactofuranose but not UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme inhibitor from a chemical library. Zebrafish embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with azides. The versatility of this technology was demonstrated by an example of selective drug delivery. These approaches have already identified several cancer biomarkers. GPI-anchored proteins play vital roles in signal transduction, the vertebrate immune response, and the pathobiology of trypanosomal parasites. Subsequently, the worms were reacted via copper-free click reaction with fluorophore-conjugated difluorinated cyclooctyne (DIFO) reagents. This assay allows for direct product detection on the membrane, obviating excessive washing and elution steps endemic to other assays. View details for Web of Science ID 000301161600025, View details for PubMedCentralID PMC3306817. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. We used this strategy to construct a paracrine signaling network in isolated 3-dimensional microtissues. We propose a model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands. Sulfotyrosine is a post-translational modification important in many extracellular protein-protein interactions, including human immunodeficiency virus infection. We report a chemical method in which the activity of an individual glycosyltransferase is controlled by a small molecule. View details for Web of Science ID 000173233300006, View details for PubMedCentralID PMC117506. View details for DOI 10.1073/pnas.2335201100, View details for Web of Science ID 000187227200045, View details for PubMedCentralID PMC299823. Here we investigate the biosynthetic origin of H. ducreyi sialosides by metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues. We provide evidence that conserved switch motifs in the G domain of CysN allosterically mediate interactions between the nucleotide binding sites. A unique response factor (R) is determined for each disaccharide, whereas a multiplexed and data processing method is incorporated for faster data acquisition and quantification purposes. We developed a new fluorophore-trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super-resolution microscopy. A., Bertozzi, C. R. Investigation of the iron-sulfur cluster in Mycobacterium tuberculosis APS reductase: Implications for substrate binding and catalysis. The importance of sulfated molecules in cell-cell communication motivated us to develop a rapid two-step method for identifying these metabolites in microorganisms, particularly in pathogenic mycobacteria. However, its superior polarity and water solubility reduced nonspecific binding, thereby improving the sensitivity of azide detection. Glycans are central to many biological processes, but efforts to define their functions at the molecular level have been frustrated by a lack of suitable technologies. Here we describe a biarylazacyclooctynone (BARAC) that has exceptional reaction kinetics and whose synthesis is designed to be both modular and scalable. Phone: (650) 721-4781. Kehoe, J. W., Maly, D. J., Verdugo, D. E., Armstrong, J. I., Cook, B. N., Ouyang, Y. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse. The approach was validated by metabolic labeling of nuclear pore protein p62, which is known to be posttranslationally modified with O-GlcNAc. Appel, M. J., Meier, K. K., Lafrance-Vanasse, J., Lim, H., Tsai, C., Hedman, B., Hodgson, K. O., Tainer, J. Some members of the family prefer previously gly co sylated peptides (ppGalNAc T7 and T10), whereas others are inhibited by neighboring gly co sy la tion (ppGalNAc T1 and T2). bertozzi@stanford.edu. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. View details for Web of Science ID 000257257100003, View details for PubMedCentralID PMC2663890. The concept of a folding funnel with kinetic traps describes folding of individual proteins. A Pictet-Spengler ligation for protein chemical modification. Here we applied the bioorthogonal chemical reporter technique for the molecular imaging of mucin-type O-glycans in live C. elegans. This technique has enabled visualization of glycans in living cells and in live organisms such as zebrafish. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. To accomplish this goal, we took advantage of the bioorthogonal chemical reporter technique. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. We used the CalFluor probes to image various alkyne-labeled biomolecules (glycans, DNA, RNA, and proteins) in cells, developing zebrafish, and mouse brain tissue slices. [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. These results establish the foundation for further development of BPDA-based colorimetric sensors. This bacterial enzyme purified from Akkermansia muciniphila cleaves N-terminally to serine and threonine residues that are modified with (preferably asialylated) O-glycans. The profile, which comprised 546 proteins, suggests diverse functions of the phagosome and potential connections to secretory processes, toll-like receptor signaling, and autophagy. Harland, C. W., Botyanszki, Z., Rabuka, D., Bertozzi, C. R., Parthasarathy, R. Crosslinking Studies of Protein-Protein Interactions in Nonribosomal Peptide Biosynthesis. Tests against related enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase. Antibody reactivity was lost by antigen treatment with sulfatase or preincubation with soluble tyrosine sulfate, indicating its specificity. The structural identification of the fragments relied on the use of a variety of radiolabeled sugar precursors, further chemical and enzymatic hydrolysis, and high-pH anion-exchange chromatography analysis. Rodriguez, E. C., Winans, K. A., King, D. S., Bertozzi, C. R. Engineered cell surfaces: Fertile ground for molecular landscaping, Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. 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. The efficacy of antimicrobial drugs against Mycobacterium tuberculosis, an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. The GlcNAc-6-0 sulfotransferase that installs the sulfate ester may be a key modulator of lymphocyte recruitment to secondary lymphoid organs and sites of chronic inflammation and is therefore a potential target for anti-inflammatory therapy.A GlcNAc-6-0-sulfotransferase activity was identified within porcine lymph nodes and characterized using a rapid, sensitive, and quantitative assay. WebShe completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. Despite their importance, few N-glycosites have been experimentally mapped in the Saccharomyces cerevisiae proteome. Kobertz, W. R., Bertozzi, C. R., Bednarski, M. D. Leukocyte adhesion - Two selectins converge on sulphate, SULFATED DISACCHARIDE INHIBITORS OF L-SELECTIN - DERIVING STRUCTURAL LEADS FROM A PHYSIOLOGICAL SELECTIN LIGAND. Sletten, E. M., Nakamura, H., Jewett, J. C., Bertozzi, C. R. Synthesis of Glycopolymers for Microarray Applications via Ligation of Reducing Sugars to a Poly(acryloyl hydrazide) Scaffold, A Strategy for the Selective Imaging of Glycans Using Caged Metabolic Precursors. Specifically, weak bases with moderate activity against M. tuberculosis (fluoxetine, sertraline, and dibucaine) were shown to accumulate intracellularly due to differential permeability and relative abundance of their ionized and nonionized forms. Zhou, X., Rodriguez-Rivera, F. P., Lim, H. C., Bell, J. C., Bernhardt, T. G., Bertozzi, C. R., Theriot, J. [37], In 2008, Bertozzi founded a startup of her own: Redwood Bioscience also in Emeryville, California. Parthasarathy, R., Rabuka, D., Bertozzi, C. R., Groves, J. T. Copper-free click chemistry for dynamic in vivo imaging. Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. View details for DOI 10.1096/fj.07-9198com, View details for Web of Science ID 000254143700018, View details for PubMedCentralID PMC2865240. Dissecting complex cellular processes requires the ability to track biomolecules as they function within their native habitat. [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. Further, enzymatically simplified N-glycans are preserved on peptides. View details for Web of Science ID 000246816400009. View details for DOI 10.1529/biophysj.107.125542, View details for Web of Science ID 000256231700017, View details for PubMedCentralID PMC2397374. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate. Analyses revealed that recurrent GBMs have increased tension and express high levels of glycoproteins that increase the bulkiness of the glycocalyx. WebProfessor 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. Bertozzi received a bachelors degree in chemistry from Harvard University in 1988 and a doctorate in the same subject from the University of California, Berkeley in 1993. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. We summarize developments in four key areas: enrichment of glycoproteins and glycopeptides from complex mixtures, emphasizing methods that exploit unique chemical properties of glycans or introduce unnatural functional groups through metabolic labeling and chemoenzymatic tagging; identification of sites of protein glycosylation; targeted glycoproteomics; and functional glycoproteomics, with a focus on probing interactions between glycoproteins and glycan-binding proteins. Proof of principle was performed by using various heparin/HS samples isolated from bovine and porcine tissues. Before joining Britannica in 2007, he worked at the University of Chicago Press on the Kara Rogers is the senior editor of biomedical sciences at Encyclopdia Britannica, where she oversees a range of content from medicine and genetics to microorganisms. These collective results provide a detailed mechanistic framework for understanding why nature chose this structurally unique monocopper active site to catalyze oxidase chemistry for sulfatase activation. This assay is 1,000-10,000 times more analytically sensitive than clinical enzyme-linked immunoassays (EIAs), displaying both 100% clinical sensitivity and 100% specificity for detecting HIV antibodies within OF samples. 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. We were able to bypass the salvage pathway by using an azide-functionalized analogue of GDP-fucose. N610 was also the primary site of sialylation of the receptor. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. This new protocol incorporates 12 known heparin disaccharides, including three sets of isomers. CD22 mediates the anti-phagocytic effect of alpha2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-beta oligomers and alpha-synuclein fibrils in vivo. Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of posttranslational modification. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. WebCarolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. 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Conformation of BARAC 's central lactam and compound reactivity and functional interrogation of SARS-CoV-2 RNA-host protein interactions steps! Her father was of Italian descent the foundation for further development of BPDA-based colorimetric sensors View details for of! Synthesis is designed to be posttranslationally modified with O-GlcNAc specific adhesive properties to the! Importance, few N-glycosites have been experimentally mapped in the physiologically relevant context of mouse!

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