Glycosphingolipid Dysregulation in Congenital Disorders of Glycysolation

Glycosphingolipid Dysregulation in Congenital Disorders of Glycysolation (CDG)

KU Leuven is an autonomous university. It was founded in 1425. It was born of and has grown within the Catholic tradition.

The project is embedded within the department of development and regeneration KU Leuven and the Laboratory of Applies Mass Spectrometry – Metabolomics expertise center. The candidate will collaborate closely with experts in clinical genetics, metabolomics, lipidomics, glycobiology and systems biology.

The research environment provides:

• Access to unique international collections of CDG patient samples
• State‑of‑the‑art mass spectrometry infrastructure
• Advanced multi‑omics platforms
• Extensive international collaborations
• Opportunities for conference participation and international training

Project

Congenital disorders of glycosylation (CDG) comprise more than 200 individually rare inherited metabolic disorders and represent one of the most rapidly expanding groups of inborn errors of metabolism. While abnormalities of protein glycosylation have traditionally been considered the primary disease mechanism, many CDG patients present with severe neurological manifestations that remain only partially understood.

Recent work from our research group has identified glycosphingolipids (GSLs), including gangliosides, as a potentially critical but underexplored disease mechanism in CDG. Because glycosphingolipids constitute the majority of glycan structures in the central nervous system and are essential for neuronal development, signalling and synaptic function, understanding their dysregulation may open entirely new therapeutic avenues.

This PhD project forms part of a larger translational research programme aimed at developing mechanism‑based treatments for CDG. The successful candidate will work at the intersection of rare disease research, neuroscience, systems biology, metabolomics and lipidomics.

Research Objectives

Objective 1 – Defining glycosphingolipid abnormalities in CDG

The candidate will perform comprehensive glycosphingolipid and ganglioside profiling in an extensive collection of patient‑derived fibroblasts representing multiple CDG subtypes. Using state‑of‑the‑art lipidomics and tracer‑based metabolomics, metabolic bottlenecks and pathway rerouting events will be identified. Treatment options will be explored.

Objective 2 – Investigating disease mechanisms and therapeutic opportunities

Key findings will be validated in neuronal‑relevant cellular models generated through CRISPR‑mediated genetic engineering and pharmacological perturbation approaches. Multi‑omics integration (lipidomics, metabolomics, proteomics and transcriptomics) will be used to identify pathogenic mechanisms and nominate therapeutic interventions, including glycosphingolipid supplementation and drug repurposing strategies.

The project builds upon unique patient cohorts, extensive preliminary data, and internationally recognised expertise in congenital disorders of glycosylation.

Profile

• Holds (or will soon obtain) a Master’s degree in Biomedical Sciences, Biology, Medicine, Bioengineering, Biochemistry, Biotechnology, Pharmaceutical Sciences, Bioinformatics or a related discipline
• Has obtained excellent academic results
• Demonstrates a strong interest in rare diseases, metabolism, neuroscience or molecular medicine
• Has an interest in advanced laboratory techniques and data analysis
• Possesses strong communication and scientific writing skills
• Is able to work independently while thriving in a collaborative multidisciplinary team
• Experience with cell culture, molecular biology, mass spectrometry, bioinformatics, programming or omics technologies is considered an asset but is not mandatory

Responsibilities

• Conduct innovative research leading to a PhD degree
• Perform experiments involving cell culture, lipidomics, metabolomics and molecular biology
• Analyse and integrate complex multi‑omics datasets
• Present research findings at national and international meetings
• Publish research in high‑quality scientific journals
• Participate in national and international collaborations
• Support supervision of Master’s thesis students

Offer

KU Leuven offers a stimulating international research environment with excellent training opportunities. The successful candidate will join a dynamic team of clinicians, PhD students, postdoctoral researchers and technicians working on rare metabolic diseases and translational therapeutic development.

Successful completion of the programme will lead to the degree of Doctor of Biomedical Sciences.

Funding and Appointment

• Fully funded PhD position (4‑year trajec