Golgi trafficking and glycosylation: From human disease to computational modelling

Activity: Talk or presentationInvited talk


Glycan processing is organized in the mammalian Golgi apparatus by sorting processing enzymes into the Golgi’s various cisternae by the use of transport vesicles. Faults in this vesicle transport process cause glycosylation defects in model organisms and congenital disorders in humans. It is not known how fine details of enzyme sorting can precisely influence glycan processing to maintain physiological states. We have started to map the alterations in the glycan patterns that result from changes in the vesicular sorting of glycosylation enzymes. For this we are using both patient derived and in vitro generated mutations in the conserved oligomeric Golgi (COG) vesicle-transport factor. Mass spectrometric glycan profiling is painting a picture in which different COG defects can have rather different subtle alterations in glycan processing. In order to understand which parts of the glycosylation machinery are altered and how, a computational model of Golgi glycan processing is being developed for the mutants. I will be discussing how patient derived mutations can inform our experiments, and how in turn our results, in particular the modelling, can in the future help to understand the patients’ molecular phenotypes.
PeriodMar 2017
Held atUCL Institute for Child Health, London, UK, United Kingdom
Degree of RecognitionNational