carolyn bertozzi biography
Dr. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at A., Bertozzi, C. R. Biomimetic bonelike composites and novel bioactive glass coatings. [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. Mechanistic and theoretical studies inspired the design of a series of cyclooctyne compounds bearing fluorine substituents, fused rings, and judiciously situated heteroatoms, with the goals of optimizing azide cycloaddition kinetics, stability, solubility, and pharmacokinetic properties. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. WebCarolyn Ruth Bertozzi (born October 10, 1966) is an American chemist. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. The use of symbols to depict glycans originated from Kornfeld in 1978, was systematized in the First Edition of "Essentials of Glycobiology" and updated for the second edition, with input from relevant organizations such as the Consortium for Functional Glycomics. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form. The azido sugars are then covalently tagged with imaging probes or epitope tags, either ex vivo or in vivo, using an azide-specific reaction. The compound was metabolized to the azidosialic acid and incorporated into cell surface and secreted sialoglycoproteins. Nevertheless, CD45 remained to be the main acceptor. 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. A., Lo, A., Codelli, J. On this Wikipedia the language links are at the top of the page across from the article title. These compounds may provide new scaffolds for extension of existing LpxC-inhibiting antibiotics to target the UDP binding pocket. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Regrettably, conventional biochemical and genetic methods often fall short for the study of glycans, because their structures are often not precisely defined at the genetic level. Thus, BARAC is a promising reagent for in vivo imaging. Photoacoustic calorimetry is shown to be a simple, precise, and accurate method for the quantification of the photophysics of a fluorescence probe, e.g., dansylamide, in a variety of solvents. Shieh, P., Siegrist, M. S., Cullen, A. J., Bertozzi, C. R. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. This strategy will prove useful for both the identification of O-GlcNAc-modified proteins and the elucidation of the specific residues that bear this saccharide. Tsai, C., Robinson, P. V., Cortez, F., Elma, M. B., Seftel, D., Pourmandi, N., Pandori, M. W., Bertozzi, C. R. Quantitative Super-Resolution Imaging Reveals Mammalian Glycocalyx Dynamics. We demonstrated that the kinetic parameters of the assembly process depend on DNA sequence complexity, density, and total cell concentration. 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. In these sulfur auxotrophs, heavy sulfate is channeled exclusively into sulfated metabolites. 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. Surprisingly, for three of the enzymes, significant activity was observed with sialylated LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in the context of sialyl Lewis x. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. In the ligation reaction, the intermediate aza-ylide undergoes intramolecular reaction with an ester, forming an amide bond faster than aza-ylide hydrolysis would otherwise occur in water. However, the complexities of glycan biosynthesis prevent the installation of nonnatural moieties at defined, predictable locations within glycoproteins at high levels of incorporation. Wisnovsky, S., Mockl, L., Malaker, S. A., Pedram, K., Hess, G. T., Riley, N. M., Gray, M. A., Smith, B. Our work provides a blueprint for a wide variety of future chemical approaches to identify, visualize, and characterize dynamic O-GlcNAc signaling. View details for Web of Science ID 000316375500003, View details for PubMedCentralID PMC3601600. Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. Together, glycomic and metabolic labeling techniques provide a comprehensive description of glycosylation as a foundation for hypothesis generation. While assays for specific glycosyltransferases exist, there is no generalizable method that can be applied across the enzyme superfamily. Kramer, J., Zhou, M., Delaveris, C., Bertozzi, C. Antibody-enzyme conjugates for targeted glycocalyx editing, Synthesis of solvatochromic probes to label the mycobacterial cell wall and their use in studies of host-pathogen interactions. 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. Vertebrate glycans constitute a large, important, and dynamic set of post-translational modifications that are notoriously difficult to manipulate and image. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. Beatty, K. E., Williams, M., Carlson, B. L., Swarts, B. M., Warren, R. M., van Helden, P. D., Bertozzi, C. R. Synthesis and Reactivity of Dibenzoselenacycloheptynes. This review highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems. [37], In 2008, Bertozzi founded a startup of her own: Redwood Bioscience also in Emeryville, California. LC-MS/MS mass spectrometry analysis was then performed and the processed data related to the identified glycoproteins show that several hundred proteins are differentially expressed between control and GALNT3 KD A2780s cells. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. In vivo, BPA appears to have greater activity than is suggested by its estrogen receptor (ER) binding affinity. Surprisingly, corneas from MyD88-/- mice displayed similar GalNAz labeling to wild-type corneas, but labeling was reduced and patchy on IL-1 receptor (IL-1R)-knockout mouse corneas (P < 0.05, ANOVA). A. View details for DOI 10.1093/glycob/cwq037, View details for Web of Science ID 000278437800004, View details for PubMedCentralID PMC2900898. The incorporation of SiaLev residues into PSA was demonstrated by protection from sialidases that can cleave natural sialic acids but not those bearing unnatural N-acyl groups. View details for DOI 10.1038/s41589-019-0342-2, View details for Web of Science ID 000525055501242, View details for Web of Science ID 000516535000056. B., Carlevaro, G., Araoz, B., Ruiz Diaz, P., Camara, M. d., Buscaglia, C. A., Bossi, M., Yu, H., Chen, X., Bertozzi, C. R., Mucci, J., Campetella, O. Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). These measurements show that the glycocalyx exhibits nanoscale organization on both cell lines and primary human tumor cells. Tian, E., Ten Hagen, K. G., SHUM, L., Hang, H. C., Imbert, Y., Young, W. W., Bertozzi, C. R., Tabak, L. A. View details for Web of Science ID 000178916000019. We have previously identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the GalNAc-transferases (GalNAc-Ts) gene family, as hypomethylated and overexpressed in high-grade serous EOC tumors, compared to low malignant potential EOC tumors and normal ovarian tissues. By contrast, only GlcNAc-6-SO(4) appears to contribute to MECA-79 binding. A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of blomolecules in living systems. Mahal, L. K., Yarema, K. J., Bertozzi, C. R. An ELISA for selectins based on binding to a physiological ligand. View details for DOI 10.1073/pnas.0710139104, View details for Web of Science ID 000251885000034, View details for PubMedCentralID PMC2154431, View details for DOI 10.1002/qsar.200740086, View details for Web of Science ID 000251832000012. Attachment via these "cell-adhesion barcodes" is rapid and specific, with close-packed arrays of cells forming within minutes. Hsiao, S. C., Crow, A. K., Lam, W. A., Bertozzi, C. R., Fletcher, D. A., Francis, M. B. Chung, S., Shin, S., Bertozzi, C. R., De Yoreo, J. J. Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by beta-Cyclodextrin. 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. Here we show that the cytosolic enzyme N-glycanase 1 (NGLY1, the human PNGase) is essential for Nrf1 activation in response to proteasome inhibition. Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Shieh, P., Dien, V. T., Beahm, B. J., Castellano, J. M., Wyss-Coray, T., Bertozzi, C. R. Isotope-targeted glycoproteomics (IsoTaG): a mass-independent platform for intact N- and O-glycopeptide discovery and analysis. A Pictet-Spengler ligation for protein chemical modification. Together, these data suggest that the expressed levels of sialylated LOS glycoforms observed in H. ducreyi are in large part controlled by the exogenous concentrations of sialic acid and at levels one might expect in vivo. Mougous, J. D., Green, R. E., Williams, S. J., Brenner, S. E., Bertozzi, C. R. Recent advances in the chemical synthesis of mucin-like glycoproteins, Conjugation of DNA to silanized colloidal semiconductor nanocrystalline quantum dots. Let us know if you have suggestions to improve this article (requires login). However, controlled investigations of the relationships between glycosylation, rigidity, and extension of membrane-bound mucins or similar macromolecules are lacking, largely because of the absence of tractable experimental models. She coined the term "bioorthogonal chemistry" for chemical reactions compatible with living systems. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. The selectins are a family of carbohydrate-binding proteins, or lectins, that have stimulated tremendous interest because of their involvement in a wide array of interactions between leukocytes and endothelial cells. Agarwal, P., Beahm, B. J., Shieh, P., Bertozzi, C. R. Live-Cell Labeling of Specific Protein Glycoforms by Proximity-Enhanced Bioorthogonal Ligation. GST-5 was also expressed in soluble epitope-tagged form and found to catalyze 6-O-sulfation of GlcNAc residues in synthetic acceptor structures. Our data show that the cysteine residue reversibly reacts with the nitrile group on the CBT moiety to form an intermediate thioimidate, which undergoes irreversible SN transfer to the lysine residue, yielding an amidine-linked product. https://www.britannica.com/biography/Carolyn-R-Bertozzi. The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. Sialylated glycans are found at elevated levels in many types of cancer and have been implicated in disease progression. Glycosylation is a prevalent, yet heterogeneous modification with a broad range of implications in molecular biology. Front-line tuberculosis (TB) drugs have been characterized extensively invitro and invivo with respect to gene expression and cell viability. View details for DOI 10.1021/acs.jproteome.6b01053. The preferred substrates and functions of the >20 isoforms in mammals are not well understood. The presence of SiaLev groups on the neuronal cell surface did not impede neurite outgrowth or significantly affect the distribution of PSA on neuronal compartments. These stratergies for cell surface 'glycoform remodeling' promise to facilitate the investigation of carbohydrate mediated cell-cell interactions. Kaushik, S., Barnes, J., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lakins, J. N., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Is the Nobel Prize in Chemistry Having a Boston Red Sox Moment? The emergence of drug-resistant Mycobacterium tuberculosis strains and the widespread occurrence of AIDS demand newer and more efficient control of tuberculosis. Marschallinger, J., Iram, T., Zardeneta, M., Lee, S. E., Lehallier, B., Haney, M. S., Pluvinage, J. V., Mathur, V., Hahn, O., Morgens, D. W., Kim, J., Tevini, J., Felder, T. K., Wolinski, H., Bertozzi, C. R., Bassik, M. C., Aigner, L., Wyss-Coray, T. Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Debets, M. F., Tastan, O. Y., Wisnovsky, S. P., Malaker, S. A., Angelis, N. n., Moeckl, L. K., Choi, J. n., Flynn, H. n., Wagner, L. J., Bineva-Todd, G. n., Antonopoulos, A. n., Cioce, A. n., Browne, W. M., Li, Z. n., Briggs, D. C., Douglas, H. L., Hess, G. T., Agbay, A. J., Roustan, C. n., Kjaer, S. n., Haslam, S. M., Snijders, A. P., Bassik, M. C., Moerner, W. E., Li, V. S., Bertozzi, C. R., Schumann, B. n. Delaveris, C. n., Wilk, A. n., Riley, N. n., Stark, J. n., Yang, S. n., Rogers, A. n., Ranganath, T. n., Nadeau, K. n., Blish, C. n., Bertozzi, C. n. Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection. The incorporation of noncanonical amino acids into recombinant proteins in Escherichia coli can be facilitated by the introduction of new aminoacyl-tRNA synthetase activity into the expression host. Hang, H. C., Yu, C., Ten Hagen, K. G., Tian, E., Winans, K. A., Tabak, L. A., Bertozzi, C. R. Probing glycosyltransferase activities with the Staudinger ligation. View details for Web of Science ID 000225233600024. Carolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. [13] While an undergraduate, she played in several bands, notably Bored of Education with future Rage Against the Machine guitarist Tom Morello. In this work, we describe the synthesis and NMR characterization of four mono- and four dideoxygenated analogs of alpha,alpha-D-trehalose. Song, J., Chen, J., Klapperich, C. M., Eng, V., Bertozzi, C. R. A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation. The phosphine-luciferin probe is therefore poised for many applications in real-time imaging in cells and whole animals. View details for Web of Science ID 000182331800019. Biological analysis of diptericin fragments indicated that the main determinant of antibacterial activity lay in the C-terminal region that is similar to the attacin peptides, although the N-terminal segment, related to the proline-rich family of antibacterial peptides, augmented that activity by 100-fold. Mounting evidence indicates that the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell activation. View details for DOI 10.1073/pnas.0307128101, View details for Web of Science ID 000187937200026, View details for PubMedCentralID PMC314150, View details for DOI 10.1002/anie.200352673, View details for Web of Science ID 000220266000010, View details for DOI 10.1002/anie.200454235, View details for Web of Science ID 000224592400009, View details for DOI 10.1002/anie.200460620, View details for Web of Science ID 000225445200005, View details for Web of Science ID 000223490500010. Symbol Nomenclature for Graphical Representations of Glycans. 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. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. Although the sulfated xenobiotics bind poorly to the ER, both stimulated the growth of receptor-positive breast tumor cells. Here we describe a method for targeting select proteins by chemical modification with a tag that imparts a distinct isotopic signature detectable in a full-scan mass spectrum. Because a sulfur auxotrophic strain is the only requirement of the approach, many microorganisms can be studied in this manner. Mougous, J. D., Leavell, M. D., Senaratne, R. H., Leigh, C. D., Williams, S. J., Riley, L. W., Leary, J. ESI-FTICR MS was utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis APS reductase. The compound potentiates the cytotoxicity of carfilzomib, a clinically used proteasome inhibitor, against MM and T cell-derived acute lymphoblastic leukemia (T-ALL) cell lines. [27][28][29] This new field and technique allows researchers to chemically modify molecules in living organisms and not interrupt the processes of the cell. [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. Bioinformatic analysis of the Mtb genome suggests the presence of a CysQ homologue encoded by the gene Rv2131c. The building block was incorporated into a synthetic peptide derived from the active site of a Mycobacterium tuberculosis sulfatase. Belardi, B., de la Zerda, A., Spiciarich, D. R., Maund, S. L., Peehl, D. M., Bertozzi, C. R. A Chemical Glycoproteomics Platform Reveals O-GlcNAcylation of Mitochondrial Voltage-Dependent Anion Channel 2. Moeckl, L., Pedram, K., Roy, A., Bertozzi, C., Moerner, W. Aebersold, R. n., Agar, J. N., Amster, I. J., Baker, M. S., Bertozzi, C. R., Boja, E. S., Costello, C. E., Cravatt, B. F., Fenselau, C. n., Garcia, B. The approach was validated by labeling a recombinant glycoprotein that is known to possess O-linked glycans with GalNAz. StcEE447D is a pan-mucin stain derived from enterohemorrhagic Escherichia coli that is tolerant to a wide range of glycoforms. 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. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. This phenomenon was first described in the early 1970s, but the molecular details underlying such transformations were poorly understood. Metabolic labeling with GalNAz followed by Staudinger ligation provides a means for proteomic analysis of this posttranslational modification and for identifying O-linked glycoprotein fingerprints associated with disease. Rabuka, D., Rush, J. S., dehart, G. W., Wu, P., Bertozzi, C. R. Cellular Microfabrication: Observing Intercellular Interactions Using Lithographically-Defined DNA Capture Sequences. View details for Web of Science ID 000222612600032. Azido sugars are fed to cells or organisms and integrated by the glycan biosynthetic machinery into various glycoconjugates. Little is known about how cells respond on a molecular level to tissue engineering scaffold materials. To differentiate sulfated from reduced-sulfur-containing molecules, we employed a mutant lacking the reductive branch of the sulfate assimilation pathway. However, a direct role for SL-1 in M. tuberculosis virulence has not been established. Oligosaccharides transact information exchange at the cell surface and modulate the activities and distribution of proteins within cells. Metabolic alterations observed during cholesterol catabolism centered on propionyl-CoA and pyruvate pools. Work, we employed a mutant lacking the reductive branch of the assembly process depend on DNA complexity. Highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems a for. 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