PhD on ERC StG DOLIGOAL – Understanding the regulation of dolichol synthesis and interactions with cholesterol metabolism

**PhD on ERC StG DOLIGOAL – Understanding the regulation of dolichol synthesis and interactions with cholesterol metabolism** ----------------------------------------------------------------------------------------------------------------------------- *(ref. BAP-2026-655)* *Laatst aangepast: 05/11/26* An ERC funded full-time PhD position is available to join the Laboratory of Prof. Matthew Wilson in the GPURE: Gynaecology, Pediatrics, Urology and Reproduction subsection of the Department of Development and Regeneration at KU Leuven, Belgium. Our laboratory focuses on human metabolism and rare inherited metabolic disorders, particularly those affecting glycosylation pathways. These ‘Congenital Disorders of Glycosylation’ (CDG) number >200 and lead to a broad range of clinical presentations such as intellectual disability, skeletal abnormalities and epilepsy. Through their study we can better diagnose patients and understand the pathological mechanisms, providing treatment targets. Furthermore, we gain profound fundamental insights into underlying biochemical pathways, with implications for more common diseases. We are situated at the heart of a world-class health sciences campus at KU Leuven, with access to numerous state-of-the-art scientific facilities. The successful candidate will also be well situated in a collaborative international context; we currently coordinate an ERDERA network (RADICAL-CDG) aimed at developing novel CDG therapies, consisting of 18 collaborators in 8 countries. ##### **Project** Through identification of a new CDG (Wilson et al. 2024 Cell; PMID 38821050), we were recently able to revise the synthesis pathway of dolichol, a lipid underlying most eukaryotic glycosylation pathways. This, amongst other findings, has profound implications for human health and disease including common diseases such as neurodegeneration and hypercholesterolaemia. We were recently awarded a European Research Council Starting Grant ‘DOLIGOAL’ (https://research.kuleuven.be/EU/p/he/p1/erc/doligoal; https://cordis.europa.eu/project/id/101300830/fr) to better understand the biochemistry and cell biology of dolichol. The successful PhD candidate will investigate a newly identified interaction between the balance of dolichol intermediates (polyisoprenoids) and the regulation of genes in the mevalonate pathway, which lies upstream of both dolichol and cholesterol metabolism. Key tasks/responsibilities will include: * Use of broad range of molecular biology techniques including DNA, RNA and protein manipulation, work with bacteria and mammalian cell lines. * The generation of cellular models using CRISPR/Cas9 gene-editing and other techniques including L2+ cell culture for lentiviral transduction of target cell lines. * Luciferase-based bespoke assay for activation assessment of the SREBP2/SCAP transcriptional regulation pathway. * Bioinformatics analysis of bulk RNASeq data to determine gene regulatory networks. * LC-MS-based