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lecture010807 - WhatisGlycobiology ,etal(circa1990)to...

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What is Glycobiology? A term frequently attributed to Raymond Dwek, et al (circa 1990) to encompass the body of research that contributes to understanding: The structure, biosynthesis, and biology of saccharides
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Or, more explicitly stated (at least more explicit than could have been imagined 25 years ago)-- Glycobiology is the human field of endeavor that strives to characterize and understand: The diversity of glycan structures The processes by which glycans are synthesized The determinants of glycan structure The mechanisms of glycan-protein interactions The impact of glycans on the structure and function of the molecules to which they are attached The contribution of glycans to normal cellular function and tissue development The participation of glycans in diverse pathologies
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Thus, aspects of glycobiology impact a broad range of disciplines To name a few-- organic synthetic chemistry neurobiology protein biochemistry reproductive medicine enzymology endocrinology analytic chemistry cell signaling structural biochemistry stem cell biology cell biology membrane biophysics developmental biology microbiology genetics cancer biology genomics immunology proteomics microbiology parasitology biotechnology And, in fact, glycobiology impacts life, itself, from conception (sperm-egg interactions) to death (apoptosis, multiple systemic pathologies)
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How do glycans impact your work? Depends on who you are: Protein biochemist: Pesky modifications that impart heterogeneity to my otherwise pure protein Structural biochemist: Nasty modifications that make it hard to crystallize some really interesting proteins Synthetic chemist: You want to synthesize what? And you want how much? Geneticist: A family of regulated molecules whose expression is not simply related to the activity of a single gene. Painful pleiotropy. Molecular Biologist: What’s the big deal--I’ve been doing glycobiology for my whole carreer? They make a nice backbone structure.
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How, then, does Glycobiology fit within the context of modern molecular, genetic, structural, and systems biology?
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The Central Dogma, circa 1970 Rather ignores a role for lipids and carbohydrates, especially at the cell surface Cell Organism DNA RNA Protein After Varki, A
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An expanded Dogma DNA RNA Protein Cell Organism enzymes Saccharides and lipids glycoconjugates Modified transcription factors After Varki, A
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Predominant cellular distribution of glycans implies role for carbohydrate in the societal interactions of cells in tissues Electron micrograph of a human lymphocyte (Ruthenium Red staining) After Varki, A
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Carbohydrates - Basic Terms Monosaccharide A carbohydrate that can not be broken down into smaller carbohydrates by treatment with acids- a simple sugar Oligosaccharide Approximately 4-12 mono units Polysaccharide Usually greater then 12 mono units Often a long linear repeating chain consiting of a single monosaccharide type with or without small side chains
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Glycoconjugates Glycoproteins
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