TDP-43 is a ubiquitously expressed DNA/RNA binding protein. It is predominantly located in the nucleus and critically regulates RNA metabolism, including transcription, splicing, stability and translation of mRNA. Mutations in its encoding gene and different post-translational protein modifications contribute to increased aggregation, enhanced cytoplasmic mislocalization and the loss of functional TDP-43 in the nucleus. Pathological TDP-43 inclusions can be found in neurons of patients with neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Frontotemporal lobar degeneration, Alzheimer’s and Parkinson’s disease. To date, the underlying molecular mechanisms and cellular receptors involved in these processes are poorly understood.

However, we have evidence that distinct serotonin receptors (5-HTRs) contribute to TDP‑43 pathology. The majority of 5-HTRs belong to the family of G protein-coupled receptors that initiate signaling pathways by activating heterotrimeric G proteins. In addition, serotonergic signaling can be mediated by G protein-independent pathways, e.g., via arrestin. The aim of this master’s thesis is therefore to investigate the influence of serotonin receptors in TDP-43 aggregation and to decipher the underlying cellular pathways.

Your Tasks:

• Biochemical investigation of TDP-43 aggregation in different cellular models (cell lines, primary neuronal cultures from mice, human iPSC-derived neurons)
• Analysis of subcellular TDP-43 localization in living cells using confocal fluorescence microscopy
• Pharmacological modulation of serotonin receptor-mediated signaling

Background required:

• Studies in natural or life science such as biochemistry, biology, biomedicine or neuroscience
• Expertise in cell culture, Western blots and microscopy

Your application:

• short 1-page CV
• Copy of BSc certificate
• Copy of high school certificate
• Transcript of Records

Please apply via email to:

labus.josephine@mh-hannover.de