Huntington’s Disease (HD) and various SpinoCerebellar Ataxia’s including SCA1 and SCA3 are inherited neurodegenerative disorders caused by the accumulation and aggregation of the polyglutamine (polyQ) expanded protein. There is no cure.

Lowering mutant huntingtin, ataxin-1 or ataxin-3 levels by improving its degradation would be a therapeutic strategy to prevent or delay onset of disease. Our recent work shows that the ubiquitin-proteasome system is capable of degrading mutant huntingtin, but that the mutation affects ubiquitination and degradation. We identified various (de)ubiquitinating enzymes interacting with the aggregation-prone huntingtin (HTT) fragments and are currently examining their role in HTT turnover, and aim to expand these strategies towards two other polyQ disorders: SCA1 and SCA3.

The project will be performed within a research group of 10 scientists including postdocs, PhD students and technicians, dedicated to improve selective mutant HTT turnover, using a combination of cell biology, biochemistry and microscopy. The team is interacting closely with the Dutch HD research network (www.huntingtonresearch.nl) and international collaborators, and embedded in the NWA CureQ consortium (www.cureq.nl).

We are looking for a postdoc researcher in our team to expand this strategy towards SCA1 and SCA3 to identify and validate the role of (de)ubiquitinating enzymes in different polyQ diseases.

Identification and validation methodologies are established technologies in the lab, and the iPSC facility is initialized and embedded in the cureQ consortium focusing on HD, SCA1 and SCA3.

In addition, you will screen for proteostasis-modulating small molecule compounds that selectively lower polyQ-expanded proteins, and validate the selectivity and mechanism-of-action of specific hits neuronal iPSC models. The high-content screening is performed in our microscopy facility embedded in our department.

• Ideally you have a PhD in neuroscience and/or proteostasis;
• Laboratory skills in biochemistry and cell biology;
• Experience with neuronal iPSC models is preferred.
• Team spirit is essential as the group works as a team, with different scientists working closely together.

• A contract for one year, to be extended after a successful evaluation in the first year.
• Salary scale 10: €3.230 to €5.088 gross for full-time employment (depending on education and experience).
• In addition to a good basic salary, you will also receive an 8.3% year-end bonus and an 8% holiday allowance.
• Pension accrual at BeFrank, a modern, understandable and fairly priced pension.
• Excellent accessibility by public transport and reimbursement of a large part of your travel costs. In addition, we have sufficient parking spaces at the AMC location and a good bicycle scheme.

Amsterdam UMC

We have a well-matched research group with analysts, OIOs and postdocs all working on improving the degradation of the Huntington's disease mutant protein. We collaborate on this with other groups in the Netherlands (www.cureQ.nl) as well as with patient associations, and internationally. In this way, the Huntington's researchers form a family with lots of meetings and interaction as well.

https://medischebiologie.nl/reits-group/