Research in the Amsterdam Leukodystrophy Center aims at improving insight into leukodystrophies and developing treatment. The disease “Megalencephalic Leukoencephalopathy with subcortical Cysts” (MLC) has been a major research focus since long. In MLC, the homeostasis of ions and water in the brain is disrupted due to a dysfunction of supportive brain cells called astrocytes. As a consequence, the brain white matter is chronically swollen starting in early childhood. Electrical activity in the brain is disturbed, and patients suffer from motor dysfunction, cognitive disability and epilepsy. There is no curative treatment for the disease.

This project aims to investigate the potential for therapeutic intervention by targeting MLC related proteins to recover astrocyte function. The PhD student will characterize novel mouse models for MLC by studying behavioral, molecular and neuropathological aspects of these models, and compare them to existing animal models. In addition, cellular studies will be performed aimed at understanding disrupted intracellular signaling that underlies astrocyte dysfunction in these models. Finally, we aim to test how small molecules can target this disrupted signaling with the ultimate goal to recover MLC phenotypes in cells and mice.

The project is a tight collaboration between the team of Dr. Rogier Min (Amsterdam Leukodystrophy Center) and the Department of Medicinal Chemistry (Prof. Rob Leurs; Vrije Universiteit Amsterdam), where high-throughput signaling assays will be performed to identify potential therapeutic compounds for MLC treatment.

What will you do:

• Familiarize yourself with astrocyte physiology in the context of MLC, and with underlying disease mechanisms;
• Familiarize yourself with existing and novel transgenic animal models for MLC;
• Characterize new models using phenotypic scoring, immunostainings and molecular tests;
• Study disease mechanisms in primary astrocyte cell culture and other cell models for MLC;
• Test whether potential therapeutic compounds identified in this project can improve MLC phenotypes in cells and animal models.

What do you bring:

We are looking for an enthusiastic PhD student, who:

• Holds a Master degree in Neurosciences, Biomedical Sciences;
• Has proven interest in the field of (cellular) neuroscience, with affinity for neurological diseases or astrocyte physiology;
• Holds an Article 9 qualification for animal experimentation;
• Is fluent in English;
• Is highly motivated;
• Can work independently and in a team;
• Has excellent communication skills;

• 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);
• Salary scale OIO: € 3.017 in the first year and increasing to € 3.824 gross based on full-time employment in the fourth year and a year-end bonus of 8.3%. Calculate your net salary here;
• Holiday hours: 186,4 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

We offer an excellent research environment. The Amsterdam Leukodystrophy Center consists of a multidisciplinary team of clinicians and laboratory researchers focusing on many different aspects of leukodystrophies. The team contains child neurologists, 6 research PI’s, trial coordinators, a post-doc, research technicians, PhD students and numerous interns. Some of us work on clinical aspects of leukodystrophies using patient registries or on clinical trials in patients. Others work in the lab and execute studies on disease mechanisms, with the aim to better understand these diseases and find openings for treatment. Working in this multidisciplinary team means that you will gain insight into many different aspects of leukodystrophies and preclinical studies.

The project is carried out in collaboration with the department of Medicinal Chemistry (Vrije Universiteit Amsterdam), where researchers study cellular signaling and work on drug design to modulate such signaling using innovative cellular assays. A PhD student in this department will closely collaborate with the PhD student that we are recruiting.

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.