Department of Neurology
Cellular Drivers of Neuroinflammation in Pneumococcal
- Institute:
- Department of Neurology
- Subject area:
- CNS infections
- Number of open position:
- 1
- Project title:
- Cellular Drivers of Neuroinflammation in Pneumococcal
- Project time plan:
- Full Doctoral Study-Model 36 months
- Language requirements:
- English (business fluent in speech and writing)
- Academic requirements:
- Completed M.Sc. in medicine/biology/biochemistry
Experience with laboratory methods such as RT-PCR, cell culture, ELISA, Western Blot, immunohistochemistry, mouse experiments (optional)
Project description:
Pneumococcal meningitis is a severe infection of the central nervous system associated with high mortality and a substantial risk of long-term neurological disability. Much of the brain damage is not caused directly by the bacteria, but by an excessive inflammatory response. While macrophages have traditionally been considered the main cells initiating this response, recent findings suggest that other cell types within the brain and its vasculature may also play important roles.
The aim of this project is to identify the key cellular regulators of inflammation during pneumococcal meningitis and to understand how these cells contribute to brain injury and treatment response. Using an established mouse model of pneumococcal meningitis, we will combine fluorescence microscopy, immunostaining with markers of selected cell populations, an NF-kB reporter mouse model and single-nucleus RNA sequencing (snRNA-seq) to determine which immune and non-immune cell populations become activated during infection. Particular attention will be given to macrophages, endothelial cells, astrocytes and pericytes.
In a second step, the functional relevance of selected cell populations will be investigated using cell-type-specific transgenic mouse models, which allow MyD88-dependent signaling to be selectively switched off in individual cell types. The project will also examine whether different murine cell populations respond differently to glucocorticoid treatment upon stimulation with pneumococci in cell culture, which may help explain why current anti-inflammatory therapy is only partially effective.
A PhD student joining this project will be integrated into the overall research program and take responsibility for defined experimental work packages. The work may include the experimental pneumococcal meningitis model, preparation and analysis of brain tissue, immunofluorescence and advanced microscopy, RT-PCR and immunoassays, as well as cell culture experiments.
The project offers the opportunity to work at the interface of neuroimmunology, infectious diseases and experimental neuroscience, with the overall goal of identifying new cellular targets for host-directed therapies in pneumococcal meningitis.
Project time plan:
| Task/Month | 1-6 | 7-12 | 13-18 | 19-24 | 25-30 | 31-36 |
|---|---|---|---|---|---|---|
| Training & experimental setup | x | |||||
| Experimental PM mouse model, snRNA-seq analysis and brain tissue analysis | x | x | x | |||
| Reporter mouse experiments and fluorescence microscops | x | x | x | x | ||
| Cell culture analyses | x | x | x | |||
| Data analyses, drafting publications and dissertation | x | x | x |
To applicants: Please send following initial application documents to LMU-CSC Office before 7th 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