Das sind wir:

The laboratory "Balancing innate immunity" (Prof. Dr. med. Roland Lang) at the Institute of Clinical Microbiology, Immunology and Hygiene of the University Hospital Erlangen offers a PhD position to investigate the function of the immunometabolite itaconate in macrophage anti-microbial activity.

Research in the Lang lab investigates how the immune system generates resistance to infection while avoiding excessive inflammation. This includes a need for efficient sensing of microbes by macrophages, generating inflammatory cytokines that direct adaptive immune responses, and regulatory mechanisms to achieve resolution of inflammation.

In collaboration with the lab of Prof. Anja Lührmann at our institute, we have investigated the host response to the intracellular bacterium Coxiella burnetii and established a mouse model to identify which immune pathways determine persistence or resolution of Q fever. The generation of the metabolite itaconate by activated macrophages is essential to restrain replication of Coxiella burnetii in macrophages and to contain early infection in vivo.

Lab homepage

• https://www.mikrobiologie.uk-erlangen.de/en/research/research-groups/research-group-of-prof-roland-lang/publications/

• Kohl, L., Hayek, I., Daniel, C., Schulze-Luhrmann, J., Bodendorfer, B., Lührmann, A., and Lang, R. (2019). MyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination. Frontiers in immunology 10, 165. Doi: 10.3389/fimmu.2019.00165
• Kohl, L., Siddique, M., Bodendorfer, B., Berger, R., Preikschat, A., Daniel, C., Olke, M., Liebler-Tenorio, E., Schulze-Luehrmann, J., Mauermeir, M., et al. (2023). Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever. EMBO Mol Med 15, e15931. Doi: 10.15252/emmm.202215931
• Lang, R., and Siddique, M. (2024). Control of immune cell signaling by the immuno-metabolite itaconate. Frontiers in immunology 15. Doi: 10.3389/fimmu.2024.1352165
• Siddique, M., Kellermeier, F., Olke, M., Zhao, M., Bussow, K., Oefner, P.J., Lührmann, A., Dettmer, K., and Lang, R. (2024). Divergent effects of itaconate isomers on Coxiella burnetii growth in macrophages and in axenic culture. Frontiers in immunology 15, 1427457. Doi: 10.3389/fimmu.2024.1427457

• The present DFG-funded project addresses the mechanisms underlying the protective effect of the ACOD1-itaconate pathway in C. burnetii infection. We aim to dissect the molecular basis of regulated uptake and intracellular transport of itaconate in infected macrophages and will address how itaconate alters anti-microbial capacities of macrophages.
• The methods employed to investigate the mechanisms will comprise in vitro infection experiments and sgRNA-based analysis of itaconate production and transport, as well as infection experiments in conditional knockout mice with cell type-specific gene deletions in the ACOD1-itaconate pathway.
• Readout systems will include multi-color flow cytometry, ELISA and multiplex cytokine analyses, protein modification and RNAseq analyses.