DC 8 - FAO in macrophage function in inflammation and immunity

• Objectives:

Aim of the project: To assess how FAO manipulation in tissue macrophages shapes their metabolic and functional programming in homeostasis and in preclinical disease models of atherosclerosis and tumour models.

1. Analyse the metabolic profile in vitro and ex vivo upon FAO manipulation in macrophages.
2. Explore how FAO controls macrophage function.
3. Study the effect of FAO induction or inhibition in TMs on tissue homeostasis and on the modulation of inflammation in the context of atherosclerosis or tumor models
4. Explore therapeutic modulation of FAO in TMs in vivo by employing liposome-based delivery strategies.

• Brief project description:

Tissue macrophages (TMs) maintain tissue homeostasis and coordinate responses to pathological challenges. Their adaptability to environmental cues enables them to meet tissue needs while preserving core functions. Importantly, most macrophage functions are closely tied to their cellular metabolism. Metabolic pathways not only provide bioenergetic support but also serve as platforms that control metabolite and redox balance and signalling. Although much research has focused on how metabolic pathways polarize macrophages in vitro, their role in macrophage polarization and impact on macrophage function within specific tissue environments is still emerging.

This project will explore how manipulating fatty acid oxidation (FAO) by targeting the rate-limiting enzyme CPT1A in TMs affects their functionality in maintaining homeostasis and in disease contexts.

• Planned secondments:

David Finlay lab (Trinity College Dublin, Irland)
• Learn click chemistry-based uptake assays to test CPT1A gain or loss of function in macrophages.

Lemonciel lab (Biocrates, Austria)
• Training on metabolomics/lipidomics techniques with application to investigate lipid profiles and lipid metabolism in TMs of genetic mouse models.

Jan van den Bossche lab (Amsterdam UMC, Netherlands)
• Training in Met-flow to study metabolic properties in TMs across different tissues in homeostasis.