PhD Microglia in Leukodystrophies

Research at the Amsterdam Leukodystrophy Center is aimed at improving insight into leukodystrophies and developing effective treatments. Leukodystrophies affect children and adults. They often cause progressive neurological disability and early death. The diseases vanishing white matter (VWM), adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), adult leukoencephalopathy with spheroids and pigmented glia (ALSP), Alexander disease and Hypomyelination are central to the Amsterdam UMC. Much post-mortem brain tissue from these diseases is available, in addition to diverse disease models.

As a PhD candidate you will work on the analysis of human post-mortem brain tissue and on disease models, such as conditional mutants. We have done a lot of research on the relative role of astrocytes and oligodendrocytes in the mechanism of various leukodystrophies. We have not yet investigated the role of microglia, while microglia probably also play an important role, which can be both positive and negative. The type of microglia disorder may provide an explanation why hematopoietic stem cell transplantation works better in some leukodystrophies than in other leukodystrophies. Determining the role of microglia in different leukodystrophies will contribute to better therapy development.

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

1. You will delve into the literature about microglia, leukodystrophies and what is known about the role of microglia in leukodystrophies. You will write a review about this.
2. The first focus is the VWM disease, where we have a lot of post-mortem brain tissue, in which microglia will be specifically examined. In complex cell cultures of different composition, you will investigate the effects of different mutant and normal cell types on each other. Microglia will be investigated in conditional and non-conditional mutant models. Conditional microglia-mutants are currently being made, which you can analyze and compare with conditional astrocyte-, oligodendrocyte- and neuron-mutant models. Taking the results of these studies together, you will make a substantial contribution to insight into the role of microglia in VWM.
3. You then examine microglia in available tissues and models of ALD, MLD, ALSP, Alexander disease and Hypomyelination and compare the outcome in these different leukodystrophies.
4. There is room for personal initiative, such as developing microglia-targeted interventions and treatments.

We are looking for an enthusiastic PhD student with:

• A medical degree or a master's degree in a field related to for example: biomedical sciences or (medical) biology;
• Demonstrable interest in medical research and an interest in neuropathology;
• Good text writing skills;
• You are able to work independently and in a team;
• Excellent communication skills; you speak fluent English.

• 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 (extension possible, subject to funding).
• Salary scale 10: € 3.493 to € 5.504 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: 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.

In the Amsterdam leukodystrophy Center, including neuropathology, we offer an excellent research environment. A multidisciplinary team focuses on many different aspects of leukodystrophies. The leukodystrophy team consists of 6 research PI’s, one post-doc, 3 child neurologists, 6 technicians, 12-16 PhD students and numerous interns. Some work on clinical aspects of the disease using several patient registries. Some work in the lab and execute studies on disease mechanisms, with the aim to better understand the disease and find openings for treatment. Some work on clinical trials in patients. We have a Leukodystrophy Brain Bank with ample material. We have different disease models.

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.