PhD Understanding and repairing astrocyte dysfunction in the leukodystrophy MLC

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;