carolyn bertozzi biography

We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. The glycan symbol nomenclature proposed by Harvey et al. Herein we describe a novel glycosyltransferase assay that exploits their unnatural substrate tolerance and the unique chemical reactivity of the azide. Since azides can be metabolically incorporated into cellular proteins and oligosaccharides, this dye may be a useful tool for profiling proteins and their posttranslational modifications. 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. Paulick, M. G., Forstner, M. B., Groves, J. T., Bertozzi, C. R. Bioorthogonal click chemistry: Covalent labeling in living systems, Redirecting lipoic acid ligase for cell surface protein labeling with small-molecule probes. View details for DOI 10.1093/glycob/cwq037, View details for Web of Science ID 000278437800004, View details for PubMedCentralID PMC2900898. View details for DOI 10.1021/jacs.5b02383, View details for Web of Science ID 000356322300038, View details for PubMedCentralID PMC4487548. Saxon, E., Luchansky, S. J., Hang, H. C., Yu, C., Lee, S. C., Bertozzi, C. R. Carbohydrate sulfotransferases of the GalNAc/Gal/GlcNAc6ST family, Kinetic analysis of NodST sulfotransferase using an electrospray ionization mass spectrometry assay. This unique technique is currently being used to investigate the enzymatic mechanism of NodST and to identify sulfotransferase inhibitors. Accordingly, treatment of cells with N-azidoacetylglucosamine results in the metabolic incorporation of the azido sugar into nuclear and cytoplasmic proteins. Front-line tuberculosis (TB) drugs have been characterized extensively invitro and invivo with respect to gene expression and cell viability. To accomplish this goal, we took advantage of the bioorthogonal chemical reporter technique. Mahal, L. K., Charter, N. W., Angata, K., Fukuda, M., Koshland, D. E., Bertozzi, C. R. Chemoselective approaches to glycoprotein assembly, A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors. View details for Web of Science ID 000171801100023. These discoveries at the forefront of biological research have motivated the design of synthetic glycoconjugates as tools for the fundamental study of glycobiology and as candidates for future generations of therapeutic and pharmaceutical reagents. The biophysical properties of the system are characterized, and the technique is used to form complex cellular patterns with single-cell line widths and self-assembled cellular microarrays. View details for Web of Science ID 000172076800007, View details for PubMedCentralID PMC60788. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications. Subcellular Partitioning and Intramacrophage Selectivity of Antimicrobial Compounds against Mycobacterium tuberculosis. 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. Methods for introducing bioorthogonal functionalities into proteins have become central to protein engineering efforts. These results demonstrate the design of macromolecules with specific orientational preferences, as well as nanometer-scale measurement of their orientation. Laughlin, S. T., Agard, N. J., Baskin, J. M., Carrico, I. S., Chang, P. V., Ganguli, A. S., Hangauer, M. J., Lo, A., Prescher, J. in these pages has relative advantages and disadvantages. The Leu-13 --> Gly (L13G) mutation is found in each of the three MetRS mutants, and the MetRS variant containing this single mutation is highly efficient in producing recombinant proteins that contain azidonorleucine. View details for Web of Science ID 000246816400009. Classic methods for monitoring glycans rely on molecular recognition with probe-bearing lectins or antibodies, but these techniques are not well suited to in vivo imaging. These stratergies for cell surface 'glycoform remodeling' promise to facilitate the investigation of carbohydrate mediated cell-cell interactions. Phagocytosis is initiated by lateral clustering of receptors, which in turn activates Src-family kinases (SFKs). Most progress has occurred in the area N-glycoproteomics. These included proteins involved in the immune response, oxidation and reduction, and vesicle transport, as well as other cellular processes. Herein we analyzed the glycopeptide substrate preferences of several ppGalNAcT family members using a library screening approach. Human cells incubated with N-levulinoylmannosamine (ManLev) process this unnatural metabolic precursor into N-levulinoyl sialic acid (SiaLev), which is incorporated into cell surface glycoconjugates. View details for Web of Science ID 000305107800004, View details for PubMedCentralID PMC3374418. View details for Web of Science ID 000173233300006, View details for PubMedCentralID PMC117506. View details for Web of Science ID 000257257100003, View details for PubMedCentralID PMC2663890. View details for DOI 10.1016/j.jmb.2006.08.080, View details for Web of Science ID 000242160600003, View details for PubMedCentralID PMC1769331. [32] Her lab has also developed tools for research. Furthermore, we demonstrate that the metabolic diversity of nature enables the use of naturally occurring functional groups that display inherent biocompatibility alongside abiotic components for organism-specific applications. The design principles embodied in coumBARAC establish a platform for generating fluorogenic cyclooctynes suited for biological imaging. Douglas, E. S., Hsiao, S. C., Onoe, H., Bertozzi, C. R., Francis, M. B., Mathies, R. A. Synthesis and Microcontact Printing of Dual End-Functionalized Mucin-like Glycopolymers for Microarray Applications. Goon, S., Schilling, B., Tullius, M. V., Gibson, B. W., Bertozzi, C. R. GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism. A., Baskin, J. M., Bertozzi, C. R., Koberstein, J. T., Turro, N. J. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). Furthermore, we show that the biosynthesis of S881 relies on the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate and a previously uncharacterized sulfotransferase, stf3. The structure, high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, and quantitative kinetic analysis, establish that the two chemically discrete steps of the overall reaction take place at distinct sites on the enzyme, mediated via conformational flexibility of the C-terminal 18 residues. O-GlcNAc transferase accepts UDP-GlcNAz as a nucleotide-sugar donor, appending an azidosugar onto its native substrates, which can then be detected by covalent labeling using azide-reactive chemical probes. Dibenzoselenacycloheptynes were prepared in three steps from commercially available reagents and trapped in situ with benzyl azide to form the corresponding triazoles. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A., Bertozzi, C. R. Isotype-specific agglutination-PCR (ISAP): Asensitive and multiplex method for measuring allergen-specific IgE. General overview of non-natural amino acid incorporation into a protein.a) Difference between normal translation (1), translation in the absence of nnAA (2) and when nnAA is supplied (3).b) The orthogonal tRNA can only work with the orthogonal aminoacyl-tRNA (aaRS) synthetase and the engineered tRNA with the engineered aaRS. Hubbard, S. C., Boyce, M., McVaugh, C. T., Peehl, D. M., Bertozzi, C. R. From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions, The Mycobacterium tuberculosis CysQ phosphatase modulates the biosynthesis of sulfated glycolipids and bacterial growth. The same mineralization technique, when applied to a hydrogel that is less prone to surface hydrolysis, led to distinctly different mineralization patterns, in terms of both the extent of mineralization and the crystallinity of the apatite grown on the hydrogel surface. We report here a strategy for the synthesis of O-linked glycopeptide analogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. 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). Phone: (650) 721-4781. B., Shieh, P., Metruccio, M. E., Evans, D. J., Bertozzi, C. R., Fleiszig, S. J. The human pathogen Mycobacterium tuberculosis (M. tb) is thought to control the human immune response with diverse biomolecules, including a variety of exotic lipids. 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. Application of the IsoTaG platform to 15 cell lines metabolically labeled with Ac4GalNAz or Ac4ManNAz revealed 1375 N- and 2159 O-glycopeptides, variously modified with 74 discrete glycan structures. Such labeled proteins can then be treated with azide-functionalized probes to ligate affinity handles or fluorophores to the PKMT substrates. Here we studied the function of novel germline variants in CSF3R at amino acid N610. [20][21], After graduating from Berkeley with a Ph.D., Bertozzi was a postdoctoral fellow at University of California, San Francisco (UCSF) with Steven Rosen, where she studied the activity of endothelial oligosaccharides in promoting cell adhesion at inflammation sites. 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. We devised an experimental model that mimics the structure of mycobacterial envelopes in which an immobile hydrophobic layer supports a TDM-rich, two-dimensionally fluid leaflet. View details for Web of Science ID 000370677300001, View details for PubMedCentralID PMC4731185, View details for DOI 10.1021/acscentsci.6b00010, View details for PubMedCentralID PMC4827666. Transposon-sequencing was then used to define its essential gene set and identify loci that, when inactivated, confer hypersensitivity to ethambutol (EMB), a drug that targets AG biogenesis. The importance and complexity associated with the totality of glycan structures, i.e. The critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote the [3 + 2] dipolar cycloaddition with azides installed metabolically into biomolecules. In this study we demonstrate that polysialyltransferases are capable of accepting unnatural substrates in terminally differentiated human neurons. These improvements represent a lowering of the limit of detection in the RASC-2 platform to 0.9 Mtb bacilli per 100L of exhaled air from 3.3 Mtb bacilli per 100L (RASC-1).This study demonstrates that technical improvements in particle collection together with sensitive detection enable rapid quantitation of viable Mtb in bioaerosols of sputum positive TB cases. Furthermore, we demonstrate that SL-1 plays a role in mediating the susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite being dispensable for maintaining overall cell envelope integrity. We report the 2.7 A resolution crystal structure of Pseudomonas aeruginosa APS reductase in the thiosulfonate intermediate form of the catalytic cycle and with substrate bound. Z. O-Pair Search with MetaMorpheus for O-glycopeptide characterization. The outlined procedure is well defined in cell culture and has been executed with over 15 cell lines. Densely O-glycosylated mucin domains are found in a broad range of cell surface and secreted proteins, where they play key physiological roles. Live cell imaging is a powerful method to study protein dynamics at the cell surface, but conventional imaging probes are bulky, or interfere with protein function, or dissociate from proteins after internalization. As a result, neurite outgrowth was similar to that observed for non-polysialylated NCAM. This left Bertozzi and the rest of the lab to complete their Ph.D. work with no direct supervision. Delaveris, C. S., Webster, E. R., Banik, S. M., Boxer, S. G., Bertozzi, C. R. Introducing "In Focus", Community Resources Accelerating Science. B., Bertozzi, C. R. Membrane proteomics of phagosomes suggests a connection to autophagy. Myristoylation is the attachment of the 14-carbon fatty acid myristate to the N-terminal glycine residue of proteins. The resulting trehalose biosynthesis mutant was unable to proliferate and enter stationary phase unless supplemented with trehalose. View details for Web of Science ID 000227308100055. Characterizing their peptide and glycopeptide substrate specificity is critical for understanding the biological role and significance of each isoform. Disruption of cysH rendered Mtb auxotrophic for cysteine and methionine, and attenuated virulence in BALB/c and C57BL/6 immunocompetent mice. Mckl, L. n., Pedram, K. n., Roy, A. R., Krishnan, V. n., Gustavsson, A. K., Dorigo, O. n., Bertozzi, C. R., Moerner, W. E. The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation. Synthetically lipidated recombinant green fluorescent protein (GFP) was shown to be stably anchored to the membrane, and its lateral fluidity was quantitatively characterized by direct fluorescence imaging in supported membranes. Bertozzi, C. R., SINGER, M. S., ROSEN, S. D. L-selectin-carbohydrate interactions: Relevant modifications of the Lewis x trisaccharide. Parthasarathy, R., Rabuka, D., Bertozzi, C. R., Groves, J. T. Copper-free click chemistry for dynamic in vivo imaging. 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Membrane proteomics of phagosomes suggests a connection to autophagy Selectivity of Compounds! Rosen, S. D. L-selectin-carbohydrate interactions: Relevant modifications of the azido sugar into nuclear and cytoplasmic proteins resulting biosynthesis! Outgrowth was similar to that observed for non-polysialylated NCAM this unique technique is currently being used to the! Of glycan structures, i.e 10.1093/glycob/cwq037, View details for DOI 10.1093/glycob/cwq037, View details for DOI,!, we show that the biosynthesis of S881 relies on the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate and previously! Being used to investigate the enzymatic mechanism of NodST and to identify sulfotransferase inhibitors, termed detection... Chemical reporter technique novel glycosyltransferase assay that exploits their unnatural substrate tolerance and the rest the. For understanding the biological role and significance of each isoform, i.e used to the...

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