PhD: GVB-Associated Resilience as a drug target for tauopathies

Intraneuronal tau pathology is a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD) and roughly one-third of frontotemporal dementia (FTD) cases. The distribution and burden of tau pathology strongly correlate with neurodegeneration and clinical symptoms, as shown by extensive postmortem and in vivo studies. Interestingly, a subset of neurons with early tau pathology contains Granulovacuolar degeneration bodies (GVBs), which have been linked to resilience against the damaging effects of tau.

Building on our discovery of this novel intrinsic neuroprotective mechanism, the GVBoost project aims to identify druggable targets and therapeutic compounds that can enhance this protective pathway. We hypothesize that boosting these intrinsic defenses offers a novel therapeutic approach. Intervening early in the disease progression may delay or even halt disease development.

Would you like to know more about the different phases within the PhD trajectory? You can read more about this on this page.

As part of this project, you will use innovative neuronal cell models and advanced molecular and cell biology techniques to achieve the following objectives:

• Identifying drug candidates suitable for repurposing that enhance neuronal resilience.
• Discovering novel druggable targets within the resilience pathway.
• Conducting proof-of-concept experiments to demonstrate that enhancing GVB-associated resilience can mitigate tau-induced neurodegeneration.

We are seeking a PhD candidate for this exciting project, funded by Hersenstichting, who has a strong passion for pursuing a career in the molecular and cell biology of dementia. Ideal candidates should have:

• A Master’s degree (MSc) in biomedical sciences or a related field, with a specialization in neuroscience.
• Proven creativity and a strong affinity for wet lab science.
• A solid background in molecular pathways and techniques, as well as experience in molecular and cell biology analyses.

• A flying start to your career in scientific research.
• Plenty of room for your drive to shape tomorrow's healthcare.
• Working on large-scale and in-house research, with motivated colleagues from all over the world.
• You will be employed by Amsterdam UMC Research BV.
• A contract for 12 months, with the intention to extend for a total of 4 years. The Guideline PhD contract applies to this vacancy.
• Salary scale OIO: € 3.108 to € 3.939 gross based on full-time employment (depending on education and experience) and a year-end bonus of 8.3%. Calculate your net salary here.
• Holiday hours: 190.4 per year for fulltime and a possibility to save additional hours.
• Pension accrual with BeFrank, a modern, comprehensible and fairly priced pension.
• For >7 km each way, 100% reimbursement for public transport travel costs and, for private transport, €0.18 per km up to a maximum of 40 km each way.
• Do you prefer walking or cycling? Take advantage of our good bike scheme. Moreover, you will receive a reimbursement of €0.18 per km.

Watch this video with more information about joining Amsterdam UMC Research BV.

Our group at Amsterdam UMC-Vrije Universiteit Amsterdam focuses on proteostatic stress mechanisms in neurodegenerative disease and is part of the center for neurogenomics and cognitive research. We use state-of-the-art molecular and cell biological technology (e.g. confocal microscopy, quantitative automated high content microcopy, proximity biotinylation etc.) and neuronal cell models for proteostatic disturbance in neurodegenerative diseases, including tau pathology and stress responses.

Here is an overview of our relevant publications:

J.F.M. Smits, T.W. Ligthart, M.Jorge-Oliva, S.Middelhoff, F. Schipper, R.Garritsen, D. Pita-Illobre., K.W. Li and W. Scheper (2025) Casein kinase 1δ-regulated formation of GVBs induces resilience to tau pathology-mediated protein synthesis impairment. Under review; BioRxiv: doi.org/10.1101/2025.03.28.645932

M. Jorge-Oliva, J. F.M. Smits, V.I. Wiersma, J.J.M. Hoozemans, W. Scheper (2022) Granulovacuolar degeneration bodies are independently induced by tau and α-synuclein pathology. Alzheimer’s Research & Therapy 14: 187 doi: 10.1186/s13195-022-01128-y

M. Jorge-Oliva, J.R.T. van Weering and W. Scheper (2023) Structurally and morphologically distinct pathological tau assemblies differentially affect GVB accumulation. International Journal of Molecular Sciences 24: 10865. doi.org/10.3390/ijms241310865

V.I. Wiersma, A.M. van Ziel, S. Vazquez-Sanchez, A. Nölle, E. Berenjeno-Correa, A. Bonaterra-Pastra, F. Clavaguera, R.J.P. Musters, J.R.T. van Weering, M. Verhage, J.J.M. Hoozemans and W. Scheper (2019) Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology. Acta Neuropathol 186: 943-970 (doi.org/10.1007/s00401-019-02046-4)

Amsterdam UMC Research BV supports non-profit scientific research. In doing so, we provide researchers with everything they need to excel. Our principal investigators (PIs) and project leaders offer support in the field of project management, finance and human resources. In medical scientific research projects, legal support is also provided.

Watch the video to find out more.

Along with your CV, please submit a motivation letter that addresses the following questions:

• Provide an example that highlights your scientific creativity.
• Share an example that demonstrates your affinity with molecular pathways.

These questions will help us gain a better understanding of your suitability for the position and your passion for scientific research.

During the publication period, applications will be handled continuously. If the vacancy is filled, it will be closed prematurely.

If you have any questions about this position, please feel free to contact Prof. dr. Wiep Scheper, Teamleader Molecular Neurodegeneration, at w.scheper@amsterdamumc.nl.

For more information about the application procedure, please contact Chey Edwards, recruitment advisor, at c.i.edwards@amsterdamumc.nl.

A reference check, screening and hiring test may be part of the procedure. Read here whether that applies to you. If you join us, we ask you for a VOG (Certificate of Good Conduct).

Internal candidates will be given priority over external candidates in case of equal suitability.

Acquisition in response to this vacancy will not be considered.