PhD researcher position: “From dolichol biosynthesis defects to glycosylation defects” (ULille and KU Leuven)

The recruited candidate will be assigned to two laboratories and teams, the Structural and Functional Glycobiology unit (UMR 8576 CNRS – ULille, Villeneuve d’Ascq, France) and the Center for Human Genetics (KU Leuven, Leuven, Belgium) as part of a Global PhD partnership between the two universities. The research will be carried out the two sites (approximately three years in France and one year in Belgium). The candidate will benefit from a high-level scientific environment in the two teams and will have all the facilities to carry out his/her research as well as access to various specific platforms. This project is part of a larger research collaboration, and meetings will be regularly organized between Lille and Leuven. Applications should include a curriculum vitae, a motivation letter and the name and contact of at least two referees.
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Project

Congenital Disorders of Glycosylation (CDG) are a rapidly growing and heterogeneous group of rare metabolic diseases caused by inborn defects in glycosylation. DHRSX has been identified as a candidate gene in CDG patients with a specific severe neurological phenotype including hypotonia, scoliosis, profound intellectual disability, epilepsy and sensorineural hearing loss. The function of DHRSX in glycosylation was not known. Our results - recently published in Cell - show that DHRSX is an oxido-reductase involved in dolichol synthesis. A DHRSX deficiency leads to polyprenol and dolichal accumulation, two compounds that now become proven intermediates in dolichol synthesis pathway. The molecular mechanisms by which the accumulation of these isoprenoid species leads to glycosylation defects remain unknown. Their elucidation constitutes the main goal of this PhD project. To tackle this intriguing pathway, we propose to investigate yeast as a model organism where our preliminary data show that Env9 is the yeast ortholog of DHRSX and that Env9 negatively interacts with Dfg10, the yeast ortholog of human SRD5A3. This PhD project shall benefit from our combined knowledge in the field of genetics, molecular and cell biology, and glycosylation, and take advantage of the availability of material from patients with specific mutations and a unique glycosylation phenotype, to fully understand the molecular function of Env9/DHRSX.

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Interested?

For more detailed information on the research project please contact Prof François FOULQUIER (francois.foulquier@univ-lille.fr) or Prof Gert MATTHIJS (gert.matthijs@kuleuven.be). Applications will be reviewed as soon as they are received and the position will be filled as soon as an ideal candidate is identified.

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