PhD Exploring enzymatic mechanisms in HTT Degradation for Drug Discovery

Huntington’s Disease (HD) is caused by a polyglutamine expansion in the disease-related HTT protein, resulting in the accumulation and aggregation of the N-terminal HTT fragment. Improving the selective degradation of this fragment would delay or prevent onset of disease, yet the HTT fragment is inefficiently ubiquitinated. To identify and manipulate involved (de)ubiquitinting enzymes we will use a ubiquitin-HTT toolbox with synthesized ubiquitinated HTT peptides with warheads to trap interacting enzymes.

Your primary base will be the Reits lab at Amsterdam UMC, were we work with a team of 10 scientists including PhD students, postdocs and technicians on various strategies to improve HTT degradation, identification and manipulation of proteins involved in degradation, develop intrabodies strategies to lower HTT and performing compound screens. We collaborate closely with the lab of Monique Mulder (LUMC), in national (Dutch HD research network and CureQ) and international networks.

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

The ZonMW project is a collaboration between the groups of Monique Mulder (LUMC) and Eric Reits (Amsterdam UMC). The project is already supported by a PhD student at the LUMC with an organic chemistry background who is developing and generating the ubiquitin-HTT toolbox for interaction studies. Your role will focus on exploring the function and mechanism-of-action of identified enzymes in HTT degradation using various available and newly-developed assays including advanced microscopy and biochemistry at the Reits lab, as well as leverage these enzymes for drug discovery through compound library screens and other state-of-the-art platforms.

We are looking for a highly motivated student with:

• A Master’s degree in cell biology, biochemistry, or a related field;
• Experience in protein degradation, enzymology, or neurodegeneration is a plus;
• A collaborative mindset and a passion for translational research.

We offer:

• The opportunity to work at the forefront of neurodegenerative disease research in two leading academic institutes;
• Access to cutting-edge tools and screening platforms;
• A multidisciplinary, collaborative environment with ample room for scientific growth.

• 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: € 3.017 to € 3.824 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.

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.

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 Eric Reits, principal investigator, via e.a.reits@amsterdamumc.nl.

For more information about the application procedure, please contact Chey Edwards, recruitment advisor, via 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 is not appreciated.