Research project
Feeding on the fat: how mycobacterial infections disrupt lipid metabolism
How do pathogenic mycobacteria alter lipid metabolism in human cells and patients, and which disrupted pathways could be targeted for new antibiotics?
- Duration
- 2025 - 2026
- Contact
- Madeline Kavanagh
- Funding
- KIEM grant (Leiden University)
Introduction
Mycobacterial infections, including tuberculosis, have caused more deaths throughout history than any other infectious disease. Treatment is lengthy, often toxic, and increasingly compromised by antibiotic resistance. Recent research shows that Mycobacterium tuberculosis exploits lipids inside human cells to survive and cause disease. Whether other pathogenic mycobacteria use similar strategies remains largely unknown. This project investigates how mycobacterial infections interfere with lipid metabolism in human cells and patients, and what this reveals about bacterial survival strategies and novel targets for drug development.
Research goal
The aim of this project is to identify biological pathways and proteins involved in lipid metabolism that are dysregulated by infection with mycobacteria, as these host proteins could serve as novel targets for antibiotic development. By combining immunology, chemistry, and clinical research, the project seeks to uncover mechanisms bacteria use to evade the immune system and to generate leads for future drug discovery.
Interdisciplinary approach
This project brings together expertise from multiple faculties and institutions. Robin van den Biggelaar (LUMC) contributes expertise in immunology and mycobacterial infections, while Madeline Kavanagh (Leiden Institute of Chemistry) specialises in mass spectrometry-based proteomics and chemical biology. The team works closely with biological collaborators at the Leiden Institute of Biology and clinical collaborators at Radboudumc, which will enable translation of laboratory findings to patient samples. This recently established collaboration connects early-career and senior researchers across disciplines and institutions.
Project description – Feeding on fat: Exploring infection-associated dysregulation of lipid metabolism
The project focuses on understanding how pathogenic mycobacteria reshape lipid metabolism in human immune cells and infected patients. Using advanced mass spectrometry techniques, the team will map changes in lipid, protein, and gene expression in infected macrophages and patient serum samples. These data will reveal which metabolic pathways are disrupted during infection and how bacteria exploit host lipids to support their growth and virulence.
Lipidomics, proteomics and transcriptomics are techniques that enable the specific type and amount of respectively lipids (fats), proteins (such as enzymes), and genes that are expressed in a sample to be studied simultaneously, at a large scale. By integrating these “omics” techniques with chemical and genetic approaches, the researchers aim to build a comprehensive picture of infection-driven metabolic changes.
These specific biological signatures could potential serve as biomarkers to monitor the progression of infectious disease, or highlight new targets for antibiotic development. Ultimately, the project will deliver a shortlist of promising biological targets that can be explored in follow-up research aimed at developing new antibiotics against drug-resistant mycobacterial infections. The results will form the basis for future PhD projects and long-term interfaculty collaboration.