carolyn bertozzi biography

Our optimized two-step enzymatic/chemical labeling scheme was used to tag and image a variety of LAP fusion proteins in multiple mammalian cell lines with diverse fluorophores including fluorescein, rhodamine, Alexa Fluor 568, ATTO 647N, and ATTO 655. Cross-linked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. A 56-member glycopeptide library designed to reflect a diversity of glycan clustering was assayed for substrate activity with ppGalNAcT isoforms using an azido-ELISA. Mauris, J., Mantelli, F., Woodward, A. M., Cao, Z., Bertozzi, C. R., Panjwani, N., Godula, K., Argueeso, P. Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains. View details for DOI 10.1073/pnas.1321205110, View details for Web of Science ID 000328858800008, View details for DOI 10.1002/anie.201307512, View details for Web of Science ID 000328531100027, View details for PubMedCentralID PMC3920747. The rapid assembly of "core 1"and "core 3" O-linked glycopeptide mimetics was accomplished in this fashion. Thus, cell assembly can be highly controlled, enabling the design of microtissues with defined cell composition and stoichiometry. View details for DOI 10.1002/anie.201508861, View details for Web of Science ID 000368061800024, View details for PubMedCentralID PMC4715665. The leukocyte adhesion molecule L-selection participates in the initial attachment of blood-borne lymphocytes to high endothelial venules (HEVs) during lymphocyte homing to secondary lymphoid organs, and contributes to leukocyte adhesion and extravasation in HEV-like vessels at sites of chronic inflammation. WebCarolyn Bertozzi is the Baker Family Director of Sarafan ChEM-H, the Anne T. and Robert M. Bass Professor of Chemistry, and a professor of chemical and systems biology and of Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA in human cells. To address this deficiency, chemists have developed technologies to perturb glycan biosynthesis, profile their presentation at the systems level, and perceive their spatial distribution. This template-driven mineralization technique provides an efficient approach toward bonelike composites with high mineral-hydrogel interfacial adhesion strength. Yu, S., Boyce, M., Wands, A. M., Bond, M. R., Bertozzi, C. R., Kohler, J. J. Elucidation and Chemical Modulation of Sulfolipid-1 Biosynthesis in Mycobacterium tuberculosis. We recently introduced a method termed isotope-targeted glycoproteomics (IsoTaG), which utilizes isotope recoding to characterize azidosugar-labeled glycopeptides bearing fully intact glycans. We demonstrate a technique for detecting magnetically labeled Listeria monocytogenes and for measuring the binding rate between antibody-linked magnetic particles and bacteria. WebIn the early 1990s, Carolyn Bertozzi began mapping a glycan that attracts immune cells to lymph nodes. In these sulfur auxotrophs, heavy sulfate is channeled exclusively into sulfated metabolites. A., Bertozzi, C. R. Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation. Sogi, K. M., Holsclaw, C. M., Fragiadakis, G. K., Nomura, D. K., Leary, J. One leads directly to the final low-energy state and the other to the kinetic trap. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. We show that by placing polar headgroups on both ends of the diacetylene lipids in a transmembranic fashion and by altering the chemical nature of the polar surface residues, the conjugated polymers can be engineered to display a range of radiation-, thermal-, and pH-induced colorimetric responses. Maturation is driven by the phosphoinositide kinase PIKfyve. We identified fluorescein-trehalose analogues that are metabolically incorporated into the trehalose mycolates of representative Mycobacterium, Corynebacterium, Nocardia, and Rhodococcus species. A., Bertozzi, C. R., Marahiel, M. A., Burkart, M. D. Uridine-Based Inhibitors as New Leads for Antibiotics Targeting Escherichia coli LpxC. Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7. Long term inhibition of mucin-type O-glycosylation, sialylation, or sulfation altered SHGFP-MUC5AC/CK characteristic diffusion time (t(1/2)), whereas all but sulfation diminished its mobile fraction. Proteasome inhibitors are used to treat blood cancers such as multiple myeloma (MM) and mantle cell lymphoma. Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion. Oligosaccharides play a crucial role in many of the recognition, signaling, and adhesion events that take place at the surface of cells. View details for DOI 10.1038/NCHEMBIO.2076, View details for Web of Science ID 000376160600017, View details for PubMedCentralID PMC4871776, View details for DOI 10.1021/acscentsci.6b00102, View details for PubMedCentralID PMC4850509. Studies of 4Fe-4S cluster stability and cysteine reactivity in the presence and absence of substrates, and in the free enzyme versus the covalent enzyme-intermediate (E-Cys-S-SO(3)(-)), suggest a structural rearrangement that occurs during the catalytic cycle. Secretory products can both diffuse, although very slowly, through the meshwork pores and interact noncovalently with the matrix. View details for Web of Science ID 000447600001778, View details for Web of Science ID 000447600001117, View details for Web of Science ID 000447609105631. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. 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. Tuberculosis (TB) disease is a global epidemic caused by the pathogenic Mycobacterium tuberculosis (Mtb). The ketone undergoes highly selective condensation reactions with complementary nucleophiles such as aminooxy and hydrazide groups. The structure reveals an unusual mode of cluster coordination by tandem cysteine residues and suggests how this arrangement might facilitate conformational change and cluster interaction with the substrate. Lemieux, G. A., Yarema, K. J., Jacobs, C. L., Bertozzi, C. R. New directions in the synthesis of glycopeptide mimetics, Probing the surface structural rearrangement of hydrogels by sum-frequency generation spectroscopy. 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. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. 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. A goal of tissue engineering is to produce a scaffold material that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. The oligonucleotides were introduced using metabolic carbohydrate engineering, which allowed reactive tailoring of the cell surface glycans for chemoselective bioconjugation. and Kirk Schanze and Lee, {T. Randall} and Lutkenhaus, {Jodie L.} and David Kaplan and Christopher Jones and Carolyn Bertozzi and Laura Kiessling and Mulcahy, {Mary Beth} and Lindsley, {Craig W.} and Finn, {M. G.} and Blum, {Joel D.} and Prashant Kamat and A., Sletten, E. M., Baskin, J. M., Miller, I. The utility of the reaction was demonstrated by selective modification of biomolecules in vitro and on living cells, with no apparent toxicity. Perez-Vilar, J., Mabolo, R., McVaugh, C. T., Bertozzi, C. R., Boucher, R. C. Molecular basis for G protein control of the prokaryotic ATP sulfurylase. We describe a method for modifying proteins site-specifically using a chemoenzymatic bioconjugation approach. A significant proportion (>45%) of the identified O-GlcNAc sites lie in close proximity to or coincide with a known phosphorylation site, supporting the potential for PTM crosstalk. 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. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. A., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., Shuken, S. R., Gate, D., Scott, M., Khatri, P., Luo, J., Bertozzi, C. R., Bassik, M. C., Wyss-Coray, T. Towards Mycobacterium tuberculosis detection at the point-of-care: solvatochromic probes permits the detection of mycobacteria within minutes, Orthogonal enzyme/substrate engineering to profile biological substrates of glycosyltransferases, Glyco-immune modulation in the tumor microenvironment, Formylglycine-generating enzyme binds substrate directly at a mononuclear Cu(I) center to initiate O-2 activation. These anchor analogues were similar in length to native GPI anchors and included mimics of the native structure's three domains. Additionally, we exploited the photolability of the QC ligation product to render the adduct cleavable with a handheld UV lamp. The Symbol Nomenclature for Glycans (SNFG) is a community-curated standard for the depiction of monosaccharides and complex glycans using various colored-coded, geometric shapes, along with defined text additions. The cyclooctynes tested displayed various labeling efficiencies that likely reflect the combined influence of intrinsic reactivity and bioavailability. Webauthor = "Burrows, {Cynthia J.} Carbohydrate biosynthetic pathways are often amenable to interception with synthetic unnatural substrates. Indeed, we showed previously that the acylation of two mitochondrial proteins at their active site cysteine residues result in their inhibition. Bouchard, G., Garcia-Marques, F. J., Karacosta, L. G., Zhang, W., Bermudez, A., Riley, N. M., Varma, S., Mehl, L. C., Benson, J. Imbert, P. R., Saric, A. n., Pedram, K. n., Bertozzi, C. R., Grinstein, S. n., Freeman, S. A. Electron-Based Dissociation Is Needed for O-Glycopeptides Derived from OpeRATOR Proteolysis. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. As a result, neurite outgrowth was similar to that observed for non-polysialylated NCAM. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Assimilatory 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductases are evolutionarily related, homologous enzymes that catalyze the same overall reaction, but do so in the absence of an [Fe-S] cluster. Here, we show that increasing sialylated glycans on cancer cells inhibits human natural killer (NK) cell activation through the recruitment of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7). 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. [17][18] While at Berkeley, she discovered that viruses can bind to sugars in the body. Mucin-type O-glycans could be imaged as early as 7 hours postfertilization, during the gastrula stage of development. [6] Her lab's development of nanotechnologies which probe biological systems lead to the development of a fast point-of-care tuberculosis test in 2018. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. Importantly, we detected increased PDIM synthesis in bacteria growing within host tissues and in bacteria grown in culture on odd-chain fatty acids. View details for DOI 10.1002/anie.201504249, View details for DOI 10.1021/jacs.5b04279, View details for Web of Science ID 000360321100003, View details for DOI 10.1021/acscentsci.5b00275, View details for PubMedCentralID PMC4827550. View details for Web of Science ID 000260193100005, View details for PubMedCentralID PMC2680727. Consistent with this view, increased levels of MMCoA led to increased abundance and mass of both PDIM and SL-1. Of the sequence motifs that are associated with 4Fe-4S centers, the cysteine dyad is atypical and has generated discussion with respect to coordination as well as the cluster's larger functional significance. Alterations in GalNAc-Ts expression were shown to provide huge variability in the O-glycoproteome in various pathologies, including cancer. View details for DOI 10.1073/pnas.1608069113. (1994) Biochemistry 33, 4830-4835] evidence is presented that (SO4-6)Gal beta 1-->4GlcNAc forms the core of a sulfated sialyl Lewis x structure that may comprise a recognition determinant on GlyCAM-1. Malaker, S. A., Pedram, K. n., Ferracane, M. J., Bensing, B. 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. Cohen, A. S., Dubikovskaya, E. A., Rush, J. S., Bertozzi, C. R. Visualizing enveloping layer glycans during zebrafish early embryogenesis. Metabolic labeling of glycans with synthetic sugar analogs has emerged as an attractive means for introducing nonnatural chemical functionality into glycoproteins. Tsui, C. K., Barfield, R. M., Fischer, C. R., Morgens, D. W., Li, A., Smith, B. The utility of this approach is demonstrated through the observation of patterned cells as they communicate by diffusion-based paracrine signaling. Selectins are central in the inflammatory response; the discovery that they bind to carbohydrate ligands has galvanized carbohydrate chemists to search for inhibitors of the process. The contributions of cell surface oligosaccharides to critical biological processes such as leukocyte-endothelial cell adhesion, bacterial and viral infection, and immunological recognition of tumor cells and foreign tissue are now understood in significant molecular detail. Despite being immunologically distinct, poly(SiaProp) can promote neurite outgrowth similarly to natural polysialic acid. Here we describe an approach for probing the galectin-induced multimerization of glycoconjugates on cultured cells. Many unique lipids and glycolipids from the Mtb cell wall are thought to be virulence factors that mediate host-pathogen interactions. We exploited StcE's unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. Mycobacterium tuberculosis (M. tuberculosis) is an intracellular pathogen possessing a complex mixture of cell wall lipids that are thought to modulate the activities of host macrophages. These receptors are promising targets for vaccine development and cancer immunotherapy. View details for Web of Science ID 000227308100055. Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. Agarwal, P., Beahm, B. J., Shieh, P., Bertozzi, C. R. Live-Cell Labeling of Specific Protein Glycoforms by Proximity-Enhanced Bioorthogonal Ligation. From 2006 to 2015 she was director of the Molecular Foundry, a nanoscience facility, at the Lawrence Berkeley National Laboratory. View details for DOI 10.1016/j.dib.2016.05.060, View details for PubMedCentralID PMC4908283. Andres, L. M., Blong, I. W., Evans, A. C., Rumachik, N. G., Yamaguchi, T., Pham, N. D., Thompson, P., Kohler, J. J., Bertozzi, C. R. Bioorthogonal Labeling of Human Prostate Cancer Tissue Slice Cultures for Glycoproteomics. Herein we report a semisynthetic method of producing membrane-anchored proteins. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. An attractive means for introducing nonnatural chemical functionality into glycoproteins as an attractive means introducing... Development of an HIV of assay based on Antibody Detection by Agglutination-PCR ( ADAP ) technology these. 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Immune checkpoint receptor Siglec-7, a nanoscience facility, at the surface of.. Adhesion events that take place at the Lawrence Berkeley National Laboratory cell assembly can be powerful tools for elucidating processes! Sugars in the O-glycoproteome in various pathologies, including cancer ligand for the glycan-binding immune checkpoint receptor Siglec-7 with. Through the observation of patterned cells as they communicate by diffusion-based paracrine signaling could be imaged as as! Mm ) and mantle cell lymphoma lymph nodes receptors are promising targets for vaccine and!