Master Thesis Project: Epitope mapping of tau repeat-domain antibodies and functional characteriz...

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Tau aggregation and propagation are key features of Alzheimer’s disease and other tauopathies. In this project, we will further characterize tau-specific antibodies reported to recognize low-n tau oligomers, with the aim of mapping their epitopes within the tau repeat domain (RD).

The student (f/m/x) will express different tau RD deletion constructs, such as variants lacking individual repeat regions, in HEK cells and assess antibody binding by Western blotting and immunofluorescence. If time permits, selected regions will be further analyzed by mutagenesis for finer epitope mapping.

In parallel, the same tau RD constructs will be tested for their ability to undergo seed-induced aggregation following exposure to exogenous tau seeds. This will initially be assessed using sedimentation assays. If time permits, stable cell lines expressing selected constructs may be generated by lentiviral transduction for image-based tau seeding assays.

Methods and techniques the student will learn:

• Mammalian cell culture of HEK cells
• Transient transfection of tau RD constructs
• Optional: lentiviral transduction and generation of stable cell populations
• Western blotting for tau construct expression and antibody binding
• Immunofluorescence staining and confocal microscopy
• Epitope mapping using deletion constructs
• Optional: site-directed mutagenesis for finer epitope mapping
• Biochemical sedimentation assays to separate soluble and insoluble tau fractions
• Image-based aggregation assays and quantification, if stable cell lines are generated

• BSc degree in Biology, Neurobiology, Cell Biology, Biochemistry, or a related field.

• Currently enrolled at a university and eligible to complete an MSc thesis as part of the degree program.

• Previous experience with basic molecular biology techniques, such as Western blotting, protein analysis, or related laboratory methods.

• Previous cell culture experience is preferred but not essential.

• Good written and spoken English communication skills.

• Careful, reliable, and well-organized approach to experimental work.

• Enthusiasm for scientific research and willingness to learn new techniques.

• Ability to work independently while also contributing effectively to a collaborative research environment.

• Good time-management skills and attention to detail.

• Motivation, curiosity, and a proactive approach to problem-solving.

Our lab is located at the German Center for Neurodegenerative Diseases (DZNE) and focuses on studying intercellular transmission of pathogenic protein aggregates in neurodegenerative diseases. The student will have the opportunity encounter to state-of-the-art methods used to investigate aggregate propagation, cellular models of neurodegeneration, and disease-relevant protein aggregation. The position offers the opportunity to work as part of an active research team and contribute to ongoing scientific projects

For further questions regarding the advertised project, please contact Dewan Al Fahad (dewanal.fahad@dzne.de). 

This research center is part of the Helmholtz Association of German Research Centers. With more than 42,000 employees and an annual budget of over € 5 billion, the Helmholtz Association is Germany's largest scientific organisation.