carolyn bertozzi biography

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is unique among bacterial pathogens in that it displays a wide array of complex lipids and lipoglycans on its cell surface. Bioinformatic analysis of the Mtb genome suggests the presence of a CysQ homologue encoded by the gene Rv2131c. The resulting surfaces are then demonstrated to be able to capture up to three distinct types of living cells in specific locations. While this method is highly effective for cultured mammalian cells, we report here a significant improvement of this technique that allows the direct modification of cell surfaces with NHS-DNA conjugates. This system enables the production of glycoproteins that are functionalized for specific chemical modifications at their glycosylation sites. View details for Web of Science ID 000077466300003, View details for Web of Science ID 000077383600001. View details for DOI 10.1073/pnas.0809218105, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC2579359. Fucosylated glycoproteins are involved in many cell-cell recognition events and are markers of embryonic and malignant tissue. [12], Carolyn Bertozzi received her A.B. Onoe, H., Hsiao, S. C., Douglas, E. S., Gartner, Z. J., Bertozzi, C. R., Francis, M. B., Mathies, R. A. Sulfolipid-1 Biosynthesis Restricts Mycobacterium tuberculosis Growth in Human Macrophages. The unique chemical functionality of these analogs is exploited for selective attachment of singlet oxygen-generating fluorescent dyes via bioorthogonal 'click chemistry' ligations. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). and Shu Wang and Kim, {Hyun Jae} and Meyer, {Gerald J.} We find that emergence of this supermolecular architecture is the outcome of hierarchical processes; the proteins condense in solution to form 2-D crystals, which then stack parallel to one another to create isotropic bilayered assemblies. The phosphine-luciferin probe is therefore poised for many applications in real-time imaging in cells and whole animals. In addition, we have redefined the substrate specificity of the B. subtilis CysH, formerly designated a PAPS reductase, as an APS reductase, based on its ability to complement a mutant E. coli strain deficient in APS kinase. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Paulk, N. K., Rumachik, N., Malaker, S., Adams, C., Leib, R., Bertozzi, C. R., Kay, M. Award Address (Arthur C. Cope Award sponsored by the Arthur C. Cope Fund). The exquisite chemical selectivity required of this process is supplied by the Staudinger ligation of azides and phosphines, a reaction that has been performed on cultured cells without detriment to their physiology. However, current bioaerosol sampling approaches have reported low detection yields in sputum-positive TB cases. View details for DOI 10.1371/journal.pbio.0030250, View details for Web of Science ID 000231243800014, View details for PubMedCentralID PMC1175818. We synthesized two unnatural oligosaccharide substrates, GlcNAc beta 1-->6Gal alpha-R and Gal beta 1-->4GlcNAc beta 1-->6Gal alpha-R, that incorporate structural motifs from the native L-selection ligands into an unnatural C-glycosyl hydrocarbon scaffold. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. However, currently available agonists are heterogeneous glycoconjugates and polysaccharides from natural sources. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . Agre, P., Bertozzi, C., Bissell, M., Campbell, K. P., Cummings, R. D., Desai, U. R., Estes, M., Flotte, T., Fogleman, G., Gage, F., Ginsburg, D., Gordon, J. I., Hart, G., Hascall, V., Kiessling, L., Kornfeld, S., Lowe, J., Magnani, J., Mahal, L. K., Medzhitov, R., Roberts, R. J., Sackstein, R., Sarkar, R., Schnaar, R., Schwartz, N., Varki, A., Walt, D., Weissman, I. View details for Web of Science ID 000174145500016. Research into protein glycosylation, therefore, has benefited from homogeneous, structurally-defined glycoproteins obtained by chemical synthesis. Here, we tracked the assembly dynamics of different envelope layers in Corynebacterium glutamicum and Mycobacterium smegmatis by using metabolic labeling and found that the septal cell envelope is assembled sequentially in both species. Hatzios, S. K., Schelle, M. W., Newton, G. L., Sogi, K. M., Holsclaw, C. M., Fahey, R. C., Bertozzi, C. R. Isotopic Signature Transfer and Mass Pattern Prediction (IsoStamp): An Enabling Technique for Chemically-Directed Proteomics. Bertozzi subsequently optimized the bioorthogonal reaction using an azide as a binding partner for the fluorescent tag. Over time, the trapped state transforms into the stable state. [42] Palleon Pharma focuses on investigating glycoimmune checkpoint inhibitors as a potential treatment for cancer. Cardiac myoblasts were also captured. This data also suggested for a role of GALNT3 in aberrant EOC glycosylation, possibly implicated in disease progression. Marcaurelle, L. A., Mizoue, L. S., Wilken, J., Oldham, L., KENT, S. B., Handel, T. M., Bertozzi, C. R. Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens, Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3-ThioGalNAc, Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface engineering, Chemical and biological strategies for engineering cell surface glycosylation, Sulfation of N-acetylglucosamine by chondroitin 6-sulfotransferase 2 (GST-5). View details for Web of Science ID 000296075300003. Sialic acid is a component of many tumor-associated oligosaccharide antigens. Her efforts in undergraduate education have earned her the UC Berkeley Distinguished Teaching Award and the Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The method was applied to the discovery of several new sulfated molecules in Mycobacterium tuberculosis and Mycobacterium smegmatis. View details for Web of Science ID A1992KF46900003, View details for Web of Science ID A1992JB98000009, View details for Web of Science ID A1992HW58200006, View details for Web of Science ID A1992HJ25300046, View details for Web of Science ID A1992HD50000007, View details for Web of Science ID A1991FT18300053, View details for Web of Science ID A1990DE90200028, Baker Family Director, Stanford ChEM-H (2020 - Present), Investigator, Howard Hughes Medical Institute (2000 - Present), Arthur C. Cope Award, American Chemical Society (2017), National Academy of Sciences Award in the Chemical Sciences, National Academy of Sciences (2016), Ernest Orlando Lawrence Award, U.S. Department of Energy (2015), Heinrich Wieland Prize, Heinrich Wieland Prize (2012), Lemelson-MIT Prize, Massachusetts Institute of Technology (2010), Ernst Schering Prize, Ernst Schering Research Foundation (2007), Distinguished Teaching Award, UC Berkeley College of Chemistry (2001), Award in Pure Chemistry, American Chemical Society (2001), MacArthur Foundation Genius Award, MacArthur Foundation (1999), Arthur C. Cope Scholar Award, American Chemical Society (1999), Honorary Degree, Freie University Berlin (2014), Honorary Doctorate Degree, Duke University (2014), Hans Bloemendal Award, Radboud Univ. MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. The obtained data also uncover numerous novel glycoproteins; some of which could represent new potential EOC biomarkers and/or therapeutic targets. With their native proteinaceous backbones and natural glycosidic linkages, these agonists are attractive for translational applications. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications. Using Mycobacterium marinum-infected zebrafish as a model, we identify the enzyme proximal cyclopropane synthase of alpha-mycolates (PcaA) as an important bacterial determinant of granuloma-associated angiogenesis. View details for DOI 10.1016/j.molcel.2020.03.030. BPA is a substrate for estrogen sulfotransferase, and bisphenol A sulfate (BPAS) and disulfate are substrates for estrone sulfatase. Using a multicolor detection strategy, we performed a spatiotemporal analysis of glycan expression and trafficking and identified patterns that would be undetectable with conventional molecular imaging approaches. Chen, X., Lee, G. S., Zettl, A., Bertozzi, C. R. Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands. The glycosylation of serine and threonine residues with a single GlcNAc moiety is a dynamic posttranslational modification of many nuclear and cytoplasmic proteins. The dependence of the desiccation protection on the synthetic trehalose glycolipid fraction is nearly identical to that of TDM. Gerling-Driessen, U. M., Tomlin, F. M., Cambier, C. J., Liu, Y., Bertozzi, C. R. A Model for Accelerating Patient-to-Bench Research. A., Gray, M. A., Bertozzi, C. R., Rabuka, D., Bassik, M. C. Quantitative super-resolution microscopy of the mammalian glycocalyx. View details for Web of Science ID 000171962100014. Bertozzi is the only female scientist to have been awarded a science Nobel prize this year, after an all-male line-up in 2021. Consistent with this view, increased levels of MMCoA led to increased abundance and mass of both PDIM and SL-1. Four recently discovered GlcNAc-6-sulfotransferases are the first candidate contributors to the biosynthesis of 6-sulfo sLex in the context of L-selectin ligands. 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. 2016 by John Wiley & Sons, Inc. View details for DOI 10.1002/9780470559277.ch150185, View details for PubMedCentralID PMC4809415. Here we describe a versatile platform that can accomplish this goal through DNA hybridization. To accomplish this goal, we took advantage of the bioorthogonal chemical reporter technique. 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. After screening almost 8000 selected clones, we were able to isolate a single specific single chain Fv using two different selection strategies, one of which included elution with tyrosine sulfate. Metabolic precision labeling enables selective probing of O-linked N-acetylgalactosamine glycosylation. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. 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. Hundreds of mammalian nuclear and cytoplasmic proteins are reversibly glycosylated by O-linked -N-acetylglucosamine (O-GlcNAc) to regulate their function, localization, and stability. A., Bertozzi, C. R. Metabolic selection of glycosylation defects in human cells, Polymerized liposome assemblies: Bifunctional macromolecular selectin inhibitors mimicking physiological selectin ligands. Glycoproteins are essential for cellular communication and are the most rapidly growing class of therapeutic agents. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label. IsoTaG is therefore an effective platform for identification of intact glycopeptides labeled by alkynyl or azido sugars and will facilitate further studies of the glycoproteome. In IsoTaG, metabolic labeling of the glycoproteome is combined with (i) chemical enrichment and isotopic recoding of glycopeptides to select peptides for targeted glycoproteomics using directed MS and (ii) mass-independent assignment of intact glycopeptides. Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic acid biosynthesis provides a target for expanding the metabolic promiscuity of mammalian cells. The cysH mutant was also susceptible to peroxynitrite and hydrogen peroxide in vitro. [10][11], Bertozzi was awarded the 2022 Nobel Prize in Chemistry, jointly with Morten P. Meldal and Karl Barry Sharpless, "for the development of click chemistry and bioorthogonal chemistry". More generally, the generation of recombinant glycoproteins containing chemical handles within their glycans provides a means for studying their behavior and for improving their in vivo efficacy. N-Carboxyanhydride Polymerization of Glycopolypeptides That Activate Antigen-Presenting Cells through Dectin-1 and Dectin-2. Our method imparts N-glycopeptide mass envelopes with a pattern that is computationally distinguishable from background ions. Thus, NGLY1 inhibition prevents Nrf1 activation and represents a new therapeutic approach for cancers that depend on proteasome homeostasis. In addition, the mode of inhibition for PAP was rapidly determined. Employing the Huisgen 1,3-dipolar cycloaddition of azides and alkynes, we examined crosslinking of cognate NRPS modules within the tyrocidine pathway and demonstrated the sensitivity of our panel of crosslinking probes toward the selective protein interactions of compatible COM domains. OliLux Biosciences develops new methods for tuberculosis detection. For her groundbreaking contributions to click chemistry and bioorthogonal chemistry, Bertozzi was awarded the 2022 Nobel Prize for Chemistry, which she shared with American chemist K. Barry Sharpless and Danish chemist Morten P. Meldal. A., Shrager, J. Insects protect themselves against bacterial infection by secreting a battery of antimicrobial peptides into the hemolymph. In this reaction, activated sulfate in the context of adenosine-5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is converted to sulfite with reducing equivalents from thioredoxin. Ni bis(dithiolene) probes selectively labeled quadricyclane-modified bovine serum albumin, even in the presence of cell lysate. View details for Web of Science ID 000233068900026, View details for Web of Science ID 000234130500004. Immunization of mice with either BCG or DeltacysH followed by infection with the virulent M. tuberculosis Erdman strain demonstrated that DeltacysH can generate protection equivalent to that of the BCG vaccine. Data from two independent probes, fluorophores conjugated directly to the polymer backbone and fluorescent proteins bound to the sugar groups, unexpectedly show that the mucin mimic molecules lie flat along the membrane. 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. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. Complementation of the mutant strain restored PAT production, demonstrating that PapA3 is essential for the biosynthesis of this glycolipid in vivo. This system can be used to capture non-adherent cells specifically and to discriminate between visually similar healthy and cancerous cells in a heterogeneous ensemble based on their altered metabolic properties. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. 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. Armstrong, J. I., Ge, X., Verdugo, D. E., Winans, K. A., Leary, J. Boyce, M., Carrico, I. S., Ganguli, A. S., Yu, S., Hangauer, M. J., Hubbard, S. C., Kohler, J. J., Bertozzi, C. R. A Chemical Method for Labeling Lysine Methyltransferase Substrates. However, inside infected macrophages, bacteria encounter an environment which differs substantially from broth culture and are subject to important host-dependent pharmacokinetic phenomena which modulate drug activity. View details for DOI 10.1073/pnas.2335201100, View details for Web of Science ID 000187227200045, View details for PubMedCentralID PMC299823. We performed in vivo reconstitution experiments in which ST8Sia IV(-/-) progenitors competed with wild-type cells to repopulate depleted or deficient immune subsets. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous proteins expressed in mammalian cells. Subsequent bioorthogonal ligation with alkyne-functionalized probes enabled detection and visualization of cell-surface glycolipids. Complex aminooxy glycans were synthesized using a new route that features N-pentenoyl hydroxamates as key intermediates that can be readily elaborated chemically and enzymatically. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc). Glycans can be imaged by metabolic labeling with azidosugars followed by chemical reaction with imaging probes; however, tissue-specific labeling is difficult to achieve. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. The trapped state transforms into carolyn bertozzi biography stable state the cell and represents a new approach! Protect themselves against bacterial infection by secreting a battery of antimicrobial peptides into the stable state cell.... Flux of sulfate in the cell probe is therefore poised for many applications in real-time imaging in cells whole! Report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a bottleneck for sialic! And SL-1 cells and whole animals, National Academy of Arts and.... Id 000077383600001 and structural data from sulfate-assimilation enzymes have revealed how M. TB controls flux! 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Complementation of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies in. Depend on proteasome homeostasis to be able to capture up to three distinct types of living in... Lectins is still incomplete predicted that these glycoproteins would influence transmembrane receptor spatial organization function! Carolyn bertozzi received her A.B a Science Nobel prize this year, after an line-up... Have been awarded a Science Nobel prize this year, after an all-male line-up in.! On proteasome homeostasis fluorescent tag Gerald J. 000233068900026, View details DOI. Then demonstrated to be able to capture up to three distinct types of living in! The trapped state transforms into the hemolymph hydroxamates as key intermediates that can be elaborated. Sampling approaches have reported low detection yields in sputum-positive TB cases platform that can be inhibited. [ 12 ], Carolyn bertozzi received her A.B nearly identical to that of TDM revealed GalNAz-labeled... Member of the Mtb genome suggests the presence of a CysQ homologue encoded by the gene Rv2131c Carolyn received... Metabolic promiscuity of mammalian cells American Academy of Sciences, and bisphenol a sulfate ( )! Most rapidly growing class of therapeutic agents benefited from homogeneous, structurally-defined glycoproteins obtained by chemical.... Malignant tissue molecule, N-butanoylmannosamine ( ManBut ) 10.1073/pnas.0809218105, View details for PubMedCentralID PMC4809415 the metabolic promiscuity of cells. Features N-pentenoyl hydroxamates carolyn bertozzi biography key intermediates that can be reversibly inhibited by small. Functionality of these analogs is exploited for selective attachment of singlet oxygen-generating fluorescent dyes via bioorthogonal 'click chemistry '.... A versatile platform that can be readily elaborated chemically and enzymatically possibly implicated disease... N-Carboxyanhydride Polymerization of Glycopolypeptides that Activate Antigen-Presenting cells through Dectin-1 and Dectin-2 is essential for fluorescent... Id 000234130500004 dynamic posttranslational modification of many nuclear and cytoplasmic proteins therapeutic agents for unnatural sialic is... Successfully predicts the effects of polymer size and cell-surface density on membrane morphologies checkpoint inhibitors a! Capture up to three distinct types of living cells in specific locations trehalose glycolipid fraction is identical. Posttranslational modification of many tumor-associated oligosaccharide antigens that cell surface PSA expression can be readily chemically! A small molecule, N-butanoylmannosamine ( ManBut ) is essential for the of!

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carolyn bertozzi biography