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Mucin glycoproteins – a complex array of carbohydrate structures

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Mucin glycoproteins – a complex array of carbohydrate structures
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Stephen Carrington talks about work that he and collaborators are undertaking to try and interrogate the complex array of carbohydrate structures present on mucin glycoproteins. These glycoproteins form part of the mucus gels that protect moist mucosal surfaces from microbial assault. Mucin glycoproteins can potentially act in two ways. Firstly, they can block the adhesins that are required for binding by harmful microbial pathogens to mucosal surfaces. Secondly, they can act as a food source for beneficial microbial colonisers that can compete with potential pathogens. We believe that these sugars represent a natural resource that can be mined for specific structures to be used to prevent harmful infections. This is because these structures represent the product of evolutionary drivers that lead to the construction of an effective barrier containing biologically engineered arrays of sugar structures that function in defense.
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MucinChemical structureDiolMeeting/Interview
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Organische ChemieSurface scienceFunctional groupMultiprotein complexKohlenhydratchemieRiver mouthCell (biology)PathogenicityMeeting/Interview
Cell (biology)Lecture/Conference
River mouthProteinKohlenhydratchemieCell (biology)Chemical structureCell membraneDiagram
Cell (biology)Cell membraneChemical structureMoleculeLecture/Conference
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Cell (biology)ThermoformingPathogenicityCell membraneThylakoidChemical structureGlycocalyxKohlenhydratchemieGlykoproteineProteinBinding energyAreaCell disruptionPathologySurface scienceMagnesium hydroxideLecture/Conference
Cell membraneSurface sciencePathologyCell disruptionInflammationLecture/Conference
Cell (biology)Surface scienceMachinabilityDiagram
GlykoproteineMultiprotein complexCell (biology)WaterKohlenhydratchemieMoleculeSurface scienceThermoformingMachinabilityProteinCell membraneGranule (cell biology)MucinSecretionLecture/Conference
ProteinMoleculeGlykoproteineKohlenhydratchemieChemical experiment
MucinLecture/ConferenceMeeting/Interview
KohlenhydratchemieAreaProcess (computing)Chain (unit)Lecture/ConferenceDiagramDrawing
KohlenhydratchemieLecture/Conference
Chain (unit)MucinKohlenhydratchemieLecture/Conference
Surface scienceChemical structureChain (unit)KohlenhydratchemieMoleculeLecture/Conference
Chemical structureLecture/Conference
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ProteinBacterial adhesinSurface scienceLecture/Conference
Host (biology)KohlenhydratchemieChemical structureSurface scienceBinding energyPolymorphism (biology)Bacterial adhesin
Binding energyChemical structureBacterial adhesinKohlenhydratchemieLecture/Conference
Binding energySystemic therapyFoodChemical structureKohlenhydratchemieMeeting/Interview
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Surface scienceProteinBacterial adhesinAdhesion
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Cell (biology)Radiation damagePathogenicityLecture/Conference
Organische ChemieFoodKohlenhydratchemieSurface scienceLecture/Conference
FoodKohlenhydratchemieLecture/Conference
Organische ChemieSurface scienceLecture/Conference
PathogenicityKohlenhydratchemieController (control theory)Surface science
Surface scienceLecture/Conference
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Transcript: English(auto-generated)
My name is Stephen Carrington and I'm Professor of Veterinary Anatomy at University College Dublin
and I'm part of a group of scientists who are interested in the interaction between microbes and complex carbohydrates present at moist mucosal surface. In order for an organism to be a pathogen, it has to penetrate a layer of cells called epithelial cells that lie over most moist
mucosal surfaces such as those found in the in the mouth or the gut or the lung and this diagram depicts those cells and there are complex structures inserted into the cell membrane which are glycoprotein molecules and these are proteins. There's about 20% protein and about 80%
carbohydrates. The carbohydrates are attached to the proteins and the glycoproteins in turn are then inserted into the cell membrane and those form a structure called the glycocalyx of the cell. And this is one of the barriers between the external environment, for example the lumen of the gut
and the cells where any pathogen would have to bind to these cells and cause disruption of the integrity of this surface epithelial membrane in order to cause pathology such as inflammation of the gut or or diarrhoea. That is one barrier. There are also
incorporated into this epithelial surface cells that are called goblet cells and those goblet cells are little machines to produce other glycoproteins. Those glycoproteins called mucins are packed into these large secretory granules and they're exported to the surface of the membrane where they suck up lots of water and they form a complex layer of
gel like material called mucus over the surface of the cell. And mucus is made up of molecules of mucin and those mucins are long linear glycoproteins. These are proteins that are decorated with sugar molecules
and if we just blow some of those mucins up you can see that they form their long linear molecules with carbohydrate chains that stick out in all directions and their job is to present carbohydrates to the external environment and those are actually the first barrier that a microbe might encounter on its way to trying to cause
problems with these epithelia. And if we blow that up again, we can see these chains of sugars that are attached to the mucin molecule and those are the structures that we're interested in and we're interested in them because microbes use them for two purposes. They have on their surface, if I just depict a microbe here and show
this is meant to depict a protein on the surface of the microbe called an adhesin. There are a number of different variants of these adhesins and there's a kind of evolutionary battle going on between the host who is trying to produce different carbohydrate structures and the microbes that are trying to produce different carbohydrates to bind to them. Those
microbes use this system, this adhesin binding system to bind to carbohydrates for two purposes. The first of those is to stabilize their niche to allow them to bind to the mucus gel and to live in it and the second thing is to help
them harvest these structures to use as a food source and so the intention of this research is basically to take these carbohydrate structures and analyze them and map them back to the proteins on the surface of the microbes that are involved in binding them
so that we fully understand this interaction. Through doing that we can then synthesize similar structures and use them as decoys to block these adhesins to prevent the microbes from colonizing the surface. If we flip the coin over and say actually most microbes that colonize moist mucosal surfaces are actually good guys and you'll all be familiar with the term of
friendly bacteria. Friendly bacteria are organisms that normally colonize mucosal surfaces and they can compete with the pathogens and prevent their colonization. So there's an interplay between pathogens that want to penetrate through to the cells and cause damage and these
so-called commensal organisms that live within the gel and those organisms actually use the carbohydrates as a food source. They harvest them, they essentially eat them. So you can promote the colonization of mucosal surfaces with friendly organisms by giving them
carbohydrates that they like to eat and so these are the two possible strategies that we can use to control pathogen colonization at mucosal surfaces.