The Experts below are selected from a list of 2811 Experts worldwide ranked by ideXlab platform
Carolyn R Bertozzi - One of the best experts on this subject based on the ideXlab platform.
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the clinical impact of Glycobiology targeting selectins siglecs and mammalian glycans
Nature Reviews Drug Discovery, 2021Co-Authors: Benjamin A H Smith, Carolyn R BertozziAbstract:Carbohydrates - namely glycans - decorate every cell in the human body and most secreted proteins. Advances in genomics, glycoproteomics and tools from chemical biology have made Glycobiology more tractable and understandable. Dysregulated glycosylation plays a major role in disease processes from immune evasion to cognition, sparking research that aims to target glycans for therapeutic benefit. The field is now poised for a boom in drug development. As a harbinger of this activity, Glycobiology has already produced several drugs that have improved human health or are currently being translated to the clinic. Focusing on three areas - selectins, Siglecs and glycan-targeted antibodies - this Review aims to tell the stories behind therapies inspired by glycans and to outline how the lessons learned from these approaches are paving the way for future Glycobiology-focused therapeutics.
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werner reutter a visionary pioneer in molecular Glycobiology
ChemBioChem, 2017Co-Authors: Stephan Hinderlich, Carolyn R Bertozzi, Rudolf Tauber, Christian P R HackenbergerAbstract:A creative pioneer: Werner Reutter (1937-2016) was a scientist who both made fundamental discoveries in Glycobiology and reached out to disciplines beyond his core field. Many of his former colleagues and students will remember his desire to exchange research ideas, which ultimately contributed to the birth of new research fields.
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symbol nomenclature for glycan representation
Proteomics, 2009Co-Authors: Ajit Varki, Richard D. Cummings, Carolyn R Bertozzi, Hudson H. Freeze, Jeffrey D Esko, Pamela Stanley, Gerald W Hart, Jamey D Marth, M E EtzlerAbstract:The glycan symbol nomenclature proposed by Harvey et al. in these pages has relative advantages and disadvantages. 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. We also note that >200 illustrations in the second edition have already been published using our nomenclature and are available for download at PubMed.
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synthetic Glycobiology exploits in the golgi compartment
Current Opinion in Chemical Biology, 2006Co-Authors: Jennifer L Czlapinski, Carolyn R BertozziAbstract:The challenge of engineering glycosylation has been confronted by synthetic chemists, biochemists and cell biologists, each with the primary goal of optimizing glycoconjugates for therapeutic applications. In nature, glycans are constructed by glycosyltransferases that are organized in an assembly line in the endoplasmic reticulum and Golgi compartment. Recent insights into the domain architecture, localization and regulation of glycosyltransferases have provided a platform for engineering their position within the secretory pathway and access to substrates. Using this knowledge, glycosyltransferase assembly lines have been redesigned for the production of specific glycan structures using protein engineering and chemical approaches. These efforts epitomize the emerging field of 'synthetic Glycobiology'.
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metabolic oligosaccharide engineering as a tool for Glycobiology
Current Opinion in Chemical Biology, 2003Co-Authors: Danielle H Dube, Carolyn R BertozziAbstract:Oligosaccharides transact information exchange at the cell surface and modulate the activities and distribution of proteins within cells. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. The technique of metabolic oligosaccharide engineering has been used to disrupt glycan biosynthesis, chemically modify cell surfaces, probe metabolic flux inside cells, and to identify specific glycoprotein subtypes from the proteome.
Robert Sackstein - One of the best experts on this subject based on the ideXlab platform.
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translational Glycobiology patient oriented glycoscience research
Glycobiology, 2016Co-Authors: Robert SacksteinAbstract:In his 1945 report to President Harry S. Truman entitled “Science: The Endless Frontier”, Vannever Bush, the then-Director of the USOffice of Scientific Research and Development, outlined his vision for a “National Research Foundation”, which ultimately became the “National Science Foundation”. In that document, Bush wanted to distinguish “basic research” from “applied research”, and offered a plan to create a government-sponsored funding agency to promote scientific education and to provide grants to nonprofit organizations for the pursuit of basic research: “Basic research is performedwithout thought of practical ends. It results in general knowledge and an understanding of nature and its laws. This general knowledge provides the means of answering a large number of important practical problems, though it may not give a complete specific answer to any one of them. The function of applied research is to provide such complete answers” (Bush 1945). In drawing the distinction between basic and applied research, Bush emphasized that the latter is problem-inspired. Thus, applied research expressly seeks to provide solutions to specific problems, i.e., is goal-oriented to offer “complete answers” to “practical ends”. Applied research that is devoted specifically to addressing unmet medical needs is called “translational research”. Analogous to other “-omics” (e.g., proteomics and genomics), glycomics is the comprehensive investigation of the structures, interactive pathways, and dynamic changes of glycans that impact biological systems, including both physiologic and pathologic processes. However, in the strictest sense, the term “glycomics” refers principally to the categorization/ characterization/elucidation of the structures of glycomolecules (e.g., encompassing information generated via NMR and mass spectrometry analysis), while the expression “glycosciences” focuses on how glycan structures relate to biologic and chemical processes/properties. Seamlessly bridging these two realms, there exists a discipline which I call “translational Glycobiology”, a term, which I hold, refers to glycoscience-based research that is specifically motivated by the intent to alleviate human suffering, which is distinct from types of glycomics inquiry that are not patient-oriented and, also, differs from the application of an existing glycoscience-based technique or reagent in clinical medicine simply because someone clever realized its utility in that setting. In this thematic special issue of Glycobiology, the field of translational Glycobiology is highlighted through the first-person narratives of four authors, each of whom is an experienced clinician. It is hoped that these articles will be both enlightening and entertaining, as each author was encouraged to relay their personal research journey within the pertinent historical perspective(s). These authors represent four distinct areas of clinical medicine: (i) Cell therapeutics (Sackstein); (ii) Transplant surgery (Cooper); (iii) Internal medicine/Allergy & Immunology (Bochner); and (iv) Dermatology (Maytin). The first article provides a framework to evaluate the biologic activity of glycoconjugates, reviews the discovery of the CD44 glycoform known as “HCELL”, and discusses how cell surface glycans can be custommodified to optimize cellular delivery to predetermined anatomic sites and thereby enable the application of cell-based therapeutics. The second article addresses how glycans impact solid organ transplantation, and how strategies to alter expression of critical glycan determinants may pave the way to cross-species transplantation (i.e., xenotransplantation), thus overcoming the critical shortage of organs needed to save the lives of patients with organ failure. The third article describes the discovery of a sialoadhesin now known as “Siglec-8” and how our increasing understanding of the structure and biology of this molecule is yielding novel therapies for allergy and other immunologic diseases. The fourth article reviews our current information on the complex biology of the glycosaminoglycan hyaluronic acid, and how structural modifications of this molecule can be harnessed to improve wound healing and dampen inflammation, effects far broader than its more recognized role in cosmetic applications as a spacefiller/wrinkle-remover. There is no prerequisite that investigators in translational Glycobiology possess MD degrees. Indeed, at present, most of the efforts in translational Glycobiology are being undertaken by scientists with Ph.D. degrees, essentially all of which have had prescribed preparation for careers in glycoscience. However, the contributing authors for this theme issue were chosen specifically because they are each accomplished clinicians, and, notably, because each did not have formal training in the discipline of glycoscience. Inspired to find solutions for alleviating the suffering of their patients, each clinician Glycobiology, 2016, vol. 26, no. 6, 544–545 doi: 10.1093/glycob/cww035 Introduction
Michael C Jewett - One of the best experts on this subject based on the ideXlab platform.
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cell free synthetic Glycobiology designing and engineering glycomolecules outside of living cells
Frontiers in Chemistry, 2020Co-Authors: Thapakorn Jaroentomeechai, Michael C Jewett, May N Taw, Alicia Aquino, Ninad Agashe, Sean Chung, Matthew P DelisaAbstract:Glycans and glycosylated biomolecules are directly involved in almost every biological process as well as the etiology of most major diseases. Hence, glycoscience knowledge is essential to efforts aimed at addressing fundamental challenges in understanding and improving human health, protecting the environment and enhancing energy security, and developing renewable and sustainable resources that can serve as the source of next-generation materials. While much progress has been made, there remains an urgent need for new tools that can overexpress structurally uniform glycans and glycoconjugates in the quantities needed for characterization and that can be used to mechanistically dissect the enzymatic reactions and multi-enzyme assembly lines that promote their construction. To address this technology gap, cell-free synthetic Glycobiology has emerged as a simplified and highly modular framework to investigate, prototype, and engineer pathways for glycan biosynthesis and biomolecule glycosylation outside the confines of living cells. From nucleotide sugars to complex glycoproteins, we summarize here recent efforts that harness the power of cell-free approaches to design, build, test, and utilize glyco-enzyme reaction networks that produce desired glycomolecules in a predictable and controllable manner. We also highlight novel cell-free methods for shedding light on poorly understood aspects of diverse glycosylation processes and engineering these processes toward desired outcomes. Taken together, cell-free synthetic Glycobiology represents a promising set of tools and techniques for accelerating basic glycoscience research (e.g., deciphering the "glycan code") and its application (e.g., biomanufacturing high-value glycomolecules on demand).
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synthetic Glycobiology parts systems and applications
ACS Synthetic Biology, 2020Co-Authors: Weston Kightlinger, Katherine F Warfel, Matthew P Delisa, Michael C JewettAbstract:Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering biology community. However, natural glycosylation systems are limited in the diversity of glycoproteins they can synthesize, the scale at which they can be harnessed for biotechnology, and the homogeneity of glycoprotein structures they can produce. Here we provide an overview of the emerging field of synthetic Glycobiology, the application of synthetic biology tools and design principles to better understand and engineer glycosylation. Specifically, we focus on how the biosynthetic and analytical tools of synthetic biology have been used to redesign glycosylation systems to obtain defined glycosylation structures on proteins for diverse applications in medicine, materials, and diagnostics. We review the key biological parts available to synthetic biologists interested in engineering glycoproteins to solve compelling problems in glycoscience, describe recent efforts to construct synthetic glycoprotein synthesis systems, and outline exemplary applications as well as new opportunities in this emerging space.
Matthew P Delisa - One of the best experts on this subject based on the ideXlab platform.
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cell free synthetic Glycobiology designing and engineering glycomolecules outside of living cells
Frontiers in Chemistry, 2020Co-Authors: Thapakorn Jaroentomeechai, Michael C Jewett, May N Taw, Alicia Aquino, Ninad Agashe, Sean Chung, Matthew P DelisaAbstract:Glycans and glycosylated biomolecules are directly involved in almost every biological process as well as the etiology of most major diseases. Hence, glycoscience knowledge is essential to efforts aimed at addressing fundamental challenges in understanding and improving human health, protecting the environment and enhancing energy security, and developing renewable and sustainable resources that can serve as the source of next-generation materials. While much progress has been made, there remains an urgent need for new tools that can overexpress structurally uniform glycans and glycoconjugates in the quantities needed for characterization and that can be used to mechanistically dissect the enzymatic reactions and multi-enzyme assembly lines that promote their construction. To address this technology gap, cell-free synthetic Glycobiology has emerged as a simplified and highly modular framework to investigate, prototype, and engineer pathways for glycan biosynthesis and biomolecule glycosylation outside the confines of living cells. From nucleotide sugars to complex glycoproteins, we summarize here recent efforts that harness the power of cell-free approaches to design, build, test, and utilize glyco-enzyme reaction networks that produce desired glycomolecules in a predictable and controllable manner. We also highlight novel cell-free methods for shedding light on poorly understood aspects of diverse glycosylation processes and engineering these processes toward desired outcomes. Taken together, cell-free synthetic Glycobiology represents a promising set of tools and techniques for accelerating basic glycoscience research (e.g., deciphering the "glycan code") and its application (e.g., biomanufacturing high-value glycomolecules on demand).
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synthetic Glycobiology parts systems and applications
ACS Synthetic Biology, 2020Co-Authors: Weston Kightlinger, Katherine F Warfel, Matthew P Delisa, Michael C JewettAbstract:Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering biology community. However, natural glycosylation systems are limited in the diversity of glycoproteins they can synthesize, the scale at which they can be harnessed for biotechnology, and the homogeneity of glycoprotein structures they can produce. Here we provide an overview of the emerging field of synthetic Glycobiology, the application of synthetic biology tools and design principles to better understand and engineer glycosylation. Specifically, we focus on how the biosynthetic and analytical tools of synthetic biology have been used to redesign glycosylation systems to obtain defined glycosylation structures on proteins for diverse applications in medicine, materials, and diagnostics. We review the key biological parts available to synthetic biologists interested in engineering glycoproteins to solve compelling problems in glycoscience, describe recent efforts to construct synthetic glycoprotein synthesis systems, and outline exemplary applications as well as new opportunities in this emerging space.
Pauline M Rudd - One of the best experts on this subject based on the ideXlab platform.
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translational Glycobiology from bench to bedside
Journal of the Royal Society of Medicine, 2019Co-Authors: John S Axford, Ghislain Opdenakker, Azita Alavi, Rick Cummings, Gordan Lauc, Celso A Reis, Pauline M RuddAbstract:The importance of sugars to protein function is real and is of significant clinical relevance. Technology advances enable large population studies to be carried out, shedding light on individual su...
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fc gamma receptors Glycobiology and therapeutic prospects
Journal of Inflammation Research, 2016Co-Authors: Jerrard M Hayes, Pauline M Rudd, Mark R Wormald, Gavin P DaveyAbstract:Therapeutic antibodies hold great promise for the treatment of cancer and autoimmune diseases, and developments in antibody-drug conjugates and bispecific antibodies continue to enhance treatment options for patients. Immunoglobulin (Ig) G antibodies are proteins with complex modifications, which have a significant impact on their function. The most important of these modifications is glycosylation, the addition of conserved glycans to the antibody Fc region, which is critical for its interaction with the immune system and induction of effector activities such as antibody-dependent cell cytotoxicity, complement activation and phagocytosis. Communication of IgG antibodies with the immune system is controlled and mediated by Fc gamma receptors (FcγRs), membrane-bound proteins, which relay the information sensed and gathered by antibodies to the immune system. These receptors are also glycoproteins and provide a link between the innate and adaptive immune systems. Recent information suggests that this receptor glycan modification is also important for the interaction with antibodies and downstream immune response. In this study, the current knowledge on FcγR glycosylation is discussed, and some insight into its role and influence on the interaction properties with IgG, particularly in the context of biotherapeutics, is provided. For the purpose of this study, other Fc receptors such as FcαR, FceR or FcRn are not discussed extensively, as IgG-based antibodies are currently the only therapeutic antibody-based products on the market. In addition, FcγRs as therapeutics and therapeutic targets are discussed, and insight into and comment on the therapeutic aspects of receptor glycosylation are provided.
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glycans as cancer biomarkers
Biochimica et Biophysica Acta, 2012Co-Authors: Barbara Adamczyk, Tharmala Tharmalingam, Pauline M RuddAbstract:Abstract Background Non-invasive biomarkers, such as those from serum, are ideal for disease prognosis, staging and monitoring. In the past decade, our understanding of the importance of glycosylation changes with disease has evolved. Scope of review We describe potential biomarkers derived from serum glycoproteins for liver, pancreatic, prostate, ovarian, breast, lung and stomach cancers. Methods for glycan analysis have progressed and newly developed high-throughput platform technologies have enabled the analysis of large cohorts of samples in an efficient manner. We also describe this evolution and trends to follow in the future. Major conclusions Many convincing examples of aberrant glycans associated with cancer have come about from glycosylation analyses. Most studies have been carried out to identify changes in serum glycan profiles or through the isolation and identification of glycoproteins that contain these irregular glycan structures. In a majority of cancers the fucosylation and sialylation expression are found to be significantly modified. Therefore, these aberrations in glycan structures can be utilized as targets to improve existing cancer biomarkers. General significance The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes Glycobiology as a promising field for potential biomarker identification. Furthermore, the high-throughput and reproducible nature of the chromatography platform have highlighted extensive applications in biomarker discovery and allowed integration of glycomics with other -omics fields, such as proteomics and genomics, making systems Glycobiology a reality. This article is part of a Special Issue entitled Glycoproteomics.
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concepts and principles of Glycobiology
The FASEB Journal, 1993Co-Authors: Ghislain Opdenakker, Pauline M Rudd, Chris P PontingAbstract:In biological systems oligosaccharides are normally conjugated to proteins or lipids. The heterogeneity and branching of oligosaccharides allow glycoconjugates to display a further level of structural and functional diversity compared with linear proteins and nucleic acids or with lipids. This review summarizes some general principles that are emerging from the new field of Glycobiology which, by addressing the molecular interactions of glycoconjugates in biological systems, spans the classical physicochemical, biological, and biochemical sciences. We discuss the genesis of glycoforms, the functional roles for glycosylation, and some general aspects of structure/function relationships with reference to N-glycosylated animal glycoproteins including the enzymes ribonuclease and tissue plasminogen activator, IgG, the family of C-type lectins, and receptor ligands.