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  3. PhD candidate "Drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome"

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PhD candidate "Drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome"

As a PhD candidate, you will study drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome (MILS). MILS is a currently untreatable …

ongeveer 2 maanden geleden

Arbeidsvoorwaarden

Standplaats:
Geert Grooteplein Zuid, Nijmegen, Gelderland
Dienstverband:
Tijdelijk contract / Tijdelijke opdracht
Uren per week:
36 - 36 uur
Salarisindicatie:
€ 2495 - € 3196 per maand
Opleidingsniveau:
WO

Functieomschrijving

As a PhD candidate, you will study drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome (MILS). MILS is a currently untreatable brain disease affecting 1/100,000 new-borns.

Mitochondria are known as the powerhouses of the cell, and their dysfunction is demonstrated in a wide variety of, often lethal, human pathologies including cancer, diabetes and aging-related neurodegeneration. For MILS, drug discovery is particularly challenging. The limited access to patient neural tissue and the impossibility to engineer mtDNA hinder the development of the cellular and animal models needed for treatment discovery.

This research project is part of the European EJP-RD consortium "CureMILS", consisting of researchers from Austria, Finland, Germany, Italy, Luxemburg, the Netherlands and Poland. CureMILS aims to develop therapies MILS and will employ neural cells generated from MILS patients via cellular reprogramming to carry out analysis of repurposable drugs, thereby allowing the identification of therapeutic strategies. Our proof-of-concept study demonstrated that this approach is feasible and relevant.

After screening 150 FDA-approved compounds, we identified phosphodiesterase 5 inhibitors (PDE5i) as a potential therapy for MILS. Compassionate use of PDE5i is now proving to be beneficial in a MILS patient. We propose to extend this approach using the largest available library of repurposable compounds (8,000). We will validate hit compounds by combining mitochondrial profiling with multi-omics analysis using reprogramming-derived neural models (neural progenitors, neurons, and brain organoids) from different MILS patients. Our consortium will identify drugs suited for repositioning as interventions in MILS, laying the foundation for a multi-national clinical trial and a concrete path towards a cure for MILS. Moreover, we will establish a paradigmatic working pipeline for reprogramming-driven drug discovery of rare neurological disorders.

At Radboudumc, research will focus on validation and mechanistic analyses of hit compounds in MILS neuronal cells. This entails elucidation of mitochondrial and functional effects of PDE5i and a selection of newly discovered compounds in NPCs and MILS neurons.

Functie-eisen

We are looking for an enthusiastic researcher (MSc) with a proven track-record in molecular biology, cellular reprogramming and/or live-cell microscopy.

Conditions

Working at Radboud university medical center means that you are ahead of the curve and working together on the healthcare of the future. But there is more. Our secondary terms of employment are impressive. These are fully tailored to you thanks to our Employment Conditions Selection Model. At Radboud university medical center, you will be given trust, and you will take the responsibility to handle everything together. We provide annual courses, both professional and personal.

The position will become available in the fourth quarter of 2021, for a duration of 3 years, and will lead to a PhD thesis.
  • In addition to your monthly salary and an annual vacation allowance of 8%, you will receive an end-of-year bonus of 8.3%.
  • If you work irregular hours, you will receive an allowance.
  • As a full-time employee (36 hours per week), you are entitled to approximately 168 vacation hours (over 23 days) per year.
  • Radboud university medical center pays 70% of the pension premium. You pay the rest of the premium with your gross salary.
  • You get a discount on health insurance as well: you can take advantage of two group health insurance plans. UMC Zorgverzekering and CZ collectief.
In addition to our terms of employment, we also offer employees various other attractive facilities, such as childcare and sports facilities. Want to learn more? Take a look at the Cao UMC.

Additional information

All additional information about the vacancy can be obtained from Dr. Werner Koopman, associate professor Biochemistry. Use the Apply button to submit your application.