Inhibiting Acute Episodic Neurological Decline in

**About the project**:
Research in the Amsterdam Leukodystrophy Center aims at improving insight into leukodystrophies and developing treatment. The disease **“vanishing white matter” (VWM)** has been a major research focus since long. VWM mostly affects children. We defined this disease 30 years ago and identified the related genes in 2001. VWM is characterized by chronic progressive neurological decline, in which patients lose neurological functions, become wheelchair-bound and die. Brain MRIs reveal increasing brain white matter abnormalities that never improve. Additionally, physical stresses, such as fever and infections, can provoke **acute episodes of neurological decline**, in which VWM patients show rapid neurological deterioration, often with lowered consciousness. Sometimes death follows, but often partial and in few cases complete recovery occurs. These acute episodes worsen overall disease progression with earlier death. With growing insight into disease mechanisms underlying chronic neurological decline, several therapeutic interventions have been developed and tested with promising results. This project aims at investigating acute episodic neurological decline, including **underlying mechanisms**, and exploring **ways to mitigate** it.

**About the role**:
You will first identify a robust animal-based model, study molecular and neuropathological changes, select quantitative markers and compare findings from the model with VWM patient data. Subsequently, the student will test FDA/EMA-approved drugs for inhibiting acute decline. Furthermore, you will:

- Familiarize yourself with VWM and underlying disease mechanisms;
- Familiarize yourself with the new models for acute neurological decline;
- Characterize new models using phenotypic scoring, immunostainings and molecular tests;
- Characterize drug treatment interventions;
- Perform essential PK/PD tests for translating the findings to human studies.

**Profile**:
We are looking for an enthusiastic PhD student, who:

- Holds a Master degree in Neurosciences, Biomedical Sciences;
- Has proven interest in the neuroscientific field, with affinity for neurological diseases or neuroinflammatory processes;
- Is Art 9 qualified;
- Is fluent in English;
- Is highly motivated;
- Can work independently and in teams and has excellent communication skills.

**Our offer**:

- 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.
- Salary scale OIO: € 3.017 to € 3.824 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.

**About the workplace**:
We offer an excellent research environment in two collaborating teams. One is a multidisciplinary team focusing on many different aspects of leukodystrophies. The leukodystrophy team consists of 6 research PI’s supported by one post-doc, trial coordinators, child neurologists, technicians, PhD students and numerous interns. Some work on clinical aspects of the disease using several 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 the disease 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.

Parts of this project will be carried out in collaboration with other specialists from Amsterdam UMC, Stanford University and patients advocacy organizations in the USA and the Netherlands.

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.

**Let's meet**:
A reference check, screening and hiring test may be part of the procedure. Read here whether that applies to you. If you join us, we ask you for a VOG (Certificate of Good Conduct).

Acquisition in response to this vacancy is not appreciated.