Seminar: Daan van Aalten

Tools to study O-GlcNAc signaling in neurodevelopment and disease

18 February 2016 11:00 hrs. - 12:00 hrs.
Location see remarks
Tools to study O-GlcNAc signaling in neurodevelopment and disease

Daan van Aalten, MRC Protein Phosphorylation and Ubiquitylation Unit and Division of Molecular Microbiology, School of Life Sciences,University of Dundee,Dundee DD1 5EH, United Kingdom


Dirk Lefeber, Dept. of Neurology, Radboudumc

18-02-2016 11:00:0018-02-2016 12:00:00Europe/AmsterdamTools to study O-GlcNAc signaling in neurodevelopment and disease Location see

Remarks / more information:


Location: Room: Aletta Jacobs (Route 802)

undefinedProtein O-GlcNAcylation is a reversible posttranslational modification of Ser/Thr on nucleocytoplasmic proteins in metazoa. This modification is essential for life at the single cell level and regulates a range of cellular processes such as metabolism, transcription, translation and signalling pathways. Defects in protein O-GlcNAcylation have been linked to diabetes, cancer and neurodegenerative disease. However, the link between O-GlcNAcylation of specific proteins and these processes/diseases remains largely unexplored.  Deletion of the O-GlcNAc transferase (OGT) or O-GlcNAc hydrolase (OGA) genes in invertebrate/vertebrate models gives rise to lethality. Using the remarkable developmental phenotypes of O-GlcNAc deficient Drosophila as a starting point, my lab is focused on discovering the O-GlcNAc proteins linked to these phenotypes, and the cellular processes involved, using a combination of chemical biology, structural biology, biochemistry and genetics. We have been the first to describe the structures and mechanisms of the OGA and OGT enzymes. We have then exploited this detailed structural knowledge to design potent inhibitors, and applied these to study the effect of modulating cellular O-GlcNAc levels and the effects on specific signalling pathways. Currently we are developing novel tools for the enrichment and MS/MS identification of O-GlcNAc proteins from Drosophila embryos and are inducing hypo-O-GlcNAcylation by means of CRISPR/Cas9 gene editing technology and the delivery of specific OGT inhibitors to identify the purveyors of the unusual Drosophila ogt developmental phenotype. These tools open avenues for further study of the involvement of O-GlcNAc in neurodegenerative/neurodevelopmental diseases.

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