- Department/Institute:
- Department of Neurology, LMU University Hospital, LMU Munich
- Subject area:
- Neuroinfections
- Name of supervisor:
- Dr. med. Susanne Dyckhoff-Shen and Prof. Uwe Ködel
- Number of open position:
- 1
- Project title:
- Regulation of macrophage function by meningeal fibroblasts in pneumococcal meningitis
- Language requirements:
- English (business fluent in speech and writing)
- Academic requirements:
- Completed M.Sc. in medicine/biology/biochemistry/
Experience with laboratory methods such as qPCR, Western Blot, cell culture, ELISA, mouse experiments (optional)
Project description:
In pneumococcal meningitis, a massive inflammatory reaction is launched by the host’s immune system to battle the pathogens leading itself to neurological damage. While the underlying molecular mechanisms have recently been elucidated, the responsible cell population within the leptomeningeal compartment remains unclear. Meningeal fibroblasts represent a large local cell population whose function has scarcely been researched to date. It was recently demonstrated that meningeal fibroblasts release selective cytokines such as IL-6, IL-8 and CCL2 upon pneumococcal challenge therefore contributing to inflammation. Moreover, their release of cytokines could be significantly increased by IL-1b in direct and indirect co-culture with macrophages. In extensive preliminary work, we were able to show that human meningeal cells prevent cell death and the activation of macrophages in the direct cell-cell contact. Pilot studies on murine meningeal cells and murine bone marrow macrophages yielded identical findings. The mechanisms behind these effects are still undefined. We hypothesized that for example the release of stress granules from meningeal cells might inhibit macrophage cell death and activation.
The main aims of this project are (i) to identify the cell-cell-interaction mechanism leading to negative feedback by MC on macrophage IL-1b production and (ii) to evaluate the effect of depleting meningeal fibroblasts (e.g. via Col1a or PDGFRα) in a murine model of pneumococcal meningitis on CNS inflammation, bacterial clearance, clinical scores and mortality in vivo.
To applicants: Please send following initial application documents to LMU-CSC Office before 15th December:
- Resume and Research Motivation Letter
- Certificate of Proficiency in English, equivalent to IELTS Test Academic 6.5 (no module below 6) or TOEFL IBT 95, is required
- Two letters of recommendation directly sent from your current Supervisors/Professors to LMU-CSC Office
Contact LMU-CSC Office: csc.international@lmu.de