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.

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

Fixed-term contract: 3 years.

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.

Radboudumc

The project will be carried out at the department of Biochemistry and the department of Pediatrics within the Radboud Institute of Molecular Life Sciences (RIMLS) of the Radboud university medical center in Nijmegen.

Research Institutes
At the moment there are more than 1,300 PhD candidates at our medical hospital. This number includes PhD candidates on our pay roll as well as external candidates (those employed somewhere else but researching on our premises).

• Radboud Institute for Health Sciences: ± 700
• Radboud Institute for Molecular Life Sciences: ± 400
• Donders Center for Medical Neurosciences: ± 200

Read what it is like to do a PhD at the Radboud University Medical Center.

Radboudumc
Radboud university medical center is a university medical center for patient care, scientific research, and education in Nijmegen. Radboud university medical center strives to be at the forefront of shaping the healthcare of the future. We do this in a person-centered and innovative way, and in close collaboration with our network. We want to have a significant impact on healthcare. We want to improve with each passing day, continuously working towards better healthcare, research, and education. And gaining a better understanding of how diseases arise and how we can prevent, treat, and cure them, day in and day out. This way, every patient always receives the best healthcare, now and in the future. Because that is why we do what we do.

Read more about our strategy and what working at Radboud university medical center means. Our colleagues would be happy to tell you about it. #weareradboudumc