DC 14 - Microbial Metabolites as Immune Metabolic Switches: Rewiring Lipid Pathways to Shape T-Cell Function

• Objectives:

Aim of the project: This project aims to define how microbiome-derived metabolites control lipid metabolism in T cells and thereby shape immune function. The goal is to uncover metabolic pathways that can be targeted to modulate inflammation and immune responses.

1. screen tissue- and microbial-derived metabolites for their impact on T-cell metabolism and function;
2. define metabolite-induced lipid remodeling in effector T cells using advanced lipidomics and single-cell metabolic profiling;
3. identify targeted lipid metabolic pathways using CRISPR/Cas9 perturbation;
4. validate immunomodulatory metabolites in human systems and preclinical inflammation models.

• Brief project description:

The microbiome produces a vast repertoire of bioactive metabolites that influence host immunity. Yet, how microbial metabolites reshape lipid metabolism in T cells—and thereby regulate immune function—remains poorly defined.

This PhD project will systematically dissect how tissue- and microbiota-derived metabolites modulate fatty acid metabolism and effector function in T cells. The candidate will perform metabolite screening to identify compounds that alter T-cell metabolic fitness, differentiation, and immune activity. Identified hits will be mechanistically characterized using advanced immunometabolic profiling platforms.

A central focus lies on defining how microbial metabolites remodel lipid composition in effector T cells. State-of-the-art lipidomics will be integrated with single-cell metabolic technologies such as SCENITH (protein translation-based metabolic profiling) and Met-Flow (flow cytometry-based mapping of metabolic enzymes). These approaches enable pathway-resolved functional analysis at high resolution. Functional consequences will be assessed using CRISPR/Cas9 genome editing and will be validated in vivo.

.Planned secondments:

Laura Bindila lab (University Medical Center of Mainz, Germany)
• Lipidomics and quantitative assays to identify lipid markers, disease mechanisms.

ActiTrexx lab,  Dr. Helmut Jonuleit, (Mainz, Germany)
• Human T cells model to study disease mechanism/biomarker and validate therapeutic targets.