Postdoc: Improving selective degradation of mutant proteins in Huntington’s Disease
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.
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.
During the publication period, applications will be handled continuously. If the vacancy is filled, it will be closed prematurely.
The first round of interviews is scheduled for the first week of October 2023. We ask you to take this into account in advance. The second round of interviews will in principle follow in mid-October.
Do you have any questions? For substantive information, please contact Eric Reits
, professor of Cellular Imaging and head of the microscopy and flow facility AmsterdamUMC location AM and group leader, via firstname.lastname@example.org
For more information about the application procedure, please contact Tanja Hart
, Recruitment Advisor, via email@example.com
or via 06-21603178
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 is not appreciated.