Towards a new era for the identification and characterisation of inborn errors of glycosylation

• Applicants: Professor Dr. Uwe Kornak; Privatdozent Dr. Christian Thiel
• Subject Area: Human Genetics
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423366611

Glycosylation is a chemical modification of proteins in our cells. It affects their stability and function. Thousands of proteins are ‘glyco-proteins’. As a result, genetic defects in glycosylation pathways lead to mostly severe diseases, called ‘Congenital Disorders of Glycosylation’ (CDG). With more than 100 different types, CDG has become an impressive group of metabolic diseases.On the one hand, we have patients with clear glycosylation anomalies, whose genetic defects remain elusive. We plan to use genomic tools to identify new genes and new disease mechanisms. On the other hand, we believe that many other patients with symptoms that fit with CDG (like intellectual disabilities, multiple congenital anomalies, bleeding disorders etc.), may have a glycosylation disorder that presently escapes diagnosis because the diagnostic tools are insufficient. We will develop new biomarkers based on glycomics, glycopeptidomics and metabolomics. In addition, fundamental research into the biochemistry of the sugars may lead to the identification of completely novel types of diseases. The ultimate goal is to treat or cure CDG patients. Since the cellular compartments where glycosylation occurs cannot easily be reached with therapeutic compounds, a causative treatment is difficult. Therefore, a better understanding of the pathophysiology of the different types of CDG is crucial for the development of novel therapeutic interventions. To this end we will systematically study already available cellular and mouse models using state-of-the-art omics approaches.. EUROGLYCAN-omics brings together a multidisciplinary group of clinical and basic researchers who have proven to be able to collaborate. We want to achieve the ambitious goals set here, for the sake of the patients and their families.

• DFG Programme: Research Grants
• International Connection: Belgium, Czech Republic, France, Netherlands, Spain
• Cooperation Partners: Professor Francois Foulquier, Ph.D.; Professorin Hana Hansíková, Ph.D.; Professor Dirk Lefeber, Ph.D.; Professor Gert Matthijs, Ph.D.; Professorin Dr. Belén Pérez; Professor Emile van Schaftingen, Ph.D.