We are seeking applicants for a PhD position in GPCR molecular pharmacology or molecular neuroscience to study an orphan GPCR as potential drug target in the rare genetic brain disease Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC), wherein mechanisms to regulate brain volume are disrupted. Children affected with MLC face a life of increasing motor and cognitive handicap. Drug treatment is currently unavailable for this rare disease. The orphan GPCR was recently identified by researchers of Pediatric Neurology (AUMC) as drug target in a subgroup of MLC patients. GPCRs are cell surface proteins that respond to external stimuli and considered to be exceptionally suited as drug targets.

The successful candidate will be part of a joint project between the groups Medicinal Chemistry (VU) and Pediatric Neurology (AUMC) and link the extensive GPCR expertise at VU with the world-renowned MLC expertise at the AUMC.

The aim of this project is to investigate how the orphan receptor is activated and signals, and to search for drug-like modulators at VU. At the AUMC a 2nd PhD student will investigate how the orphan GPCR is involved in brain volume regulation. To study the orphan GPCR, molecular receptor pharmacology techniques will be employed including development of cell-based bioluminescent/fluorescent biosensor assays to detect GPCR signaling events in various cellular models. Ultimately, new modulators can be tested in a variety of cellular and in vivo models of disease at the AUMC.

Your duties

• Study the signaling properties of the orphan GPCR, employing a number of innovative biosensor methodologies.
• Develop suitable assay(s) to study the modulation of the GPCR with drug-like molecules and a library of endogenous signaling molecules
• Screen libraries of FDA-approved drugs and drug-like molecules, fragments and proprietary drug libraries to discover new GPCR modulators, that can be tested in more translational models (cellular and in vivo models) with the AUMC collaborators.
• Contribute to teaching and supervising activities (including supervision of MSc and BSc students);
• Collaborate within the team with the UAMC colleagues and other international researchers;
• Publish scientific articles and present research results at international conferences and journals;
• Conduct research within the scope of the project leading to a dissertation and a PhD degree towards the end of the 4-year project.

• MSc in Pharmaceutical sciences, (Molecular) Neuroscience, Biomedical sciences, Medicinal Chemistry or a comparable life sciences degree,
• Experience in drug discovery, (molecular) receptor pharmacology, biochemistry (cell culture, radioligand binding and/or cell-based signal-transduction assays using biosensors and FRET/BRET) is highly recommended.
• Experience in molecular biology and/or microscopy is appreciated.
• Motivated and enthusiastic.
• A dedicated, flexible team player with strong communicating skills.
• Able to stimulate and motivate undergraduate students and co-workers with various backgrounds (e.g. organic and computational chemists).
• Stepping up and taking responsibility; eye for lab organization and lab safety.

Fixed-term contract: 1 year.

A challenging position in a socially involved organization. The salary will be in accordance with university regulations for academic personnel and amounts €2,541 per month during the first year and increases to €3,247 per month during the fourth year, based on a full-time employment. The job profile (PhD candidate) is based on the university job ranking system and is vacant for 1 FTE.

The appointment will initially be for 1 year. After a satisfactory evaluation of the initial appointment, the contract will be extended for a duration of 4 years.

Additionally, Vrije Universiteit Amsterdam offers excellent fringe benefits and various schemes and regulations to promote a good work/life balance, such as:

• a maximum of 41 days of annual leave based on full-time employment;
• 8% holiday allowance and 8.3% end-of-year bonus;
• solid pension scheme (ABP);
• possibility to save holiday hours, for sabbatical leave;
• child day care facilities available on campus.

Vrije Universiteit Amsterdam

The ambition of Vrije Universiteit Amsterdam is clear: to contribute to a better world through outstanding education and ground-breaking research. We strive to be a university where personal development and commitment to society play a leading role. A university where people from different disciplines and backgrounds collaborate to achieve innovations and to generate new knowledge. Our teaching and research encompass the entire spectrum of academic endeavor - from the humanities, the social sciences and the natural sciences through to the life sciences and the medical sciences.

Vrije Universiteit Amsterdam is home to more than 30,000 students. We employ over 5,500 individuals. The VU campus is easily accessible and located in the heart of Amsterdam's Zuidas district, a truly inspiring environment for teaching and research.

Diversity
We are an inclusive university community. Diversity is one of our most important values. We believe that engaging in international activities and welcoming students and staff from a wide variety of backgrounds enhances the quality of our education and research. We are always looking for people who can enrich our world with their own unique perspectives and experiences.

The Faculty of Science
Working at the Faculty of Science means working together with students, PhD candidates and scientists who are focused on their discipline, yet also have a broad view of the world. We are proud of the collegial working environment within the faculty, which is characterised by an ambitious and pragmatic attitude with commitment to the bigger picture. At the Faculty of Science, scientists and students work on fundamental and complex social issues for a sustainable and healthy future. From forest fires to big data, from obesity to malnutrition, from genetics to pharmaceuticals and from molecules to the moon: our teaching and research cover the full breadth of the natural sciences. Scientific teaching and research is highly experimental, technical, computational and interdisciplinary in nature. This is why we collaborate extensively with leading research institutes and industry. The faculty has over 11,000 students studying across 40 educational programmes and employs over 1,600 staff spread over 10 scientific departments, making us the largest science faculty in the Netherlands.

About the department of Medicinal Chemistry
The Medicinal Chemistry group is part of the Department of Chemistry and Pharmaceutical Sciences. It combines research in molecular pharmacology, biochemistry, computer-aided drug design and chemical synthesis to acquire detailed insight into molecular interactions between drug targets and biological active molecules (drug-like compounds and nanobodies). Moreover, we are interested in modulation of cellular signalling by these biological active molecules. The division has a strong history in GPCR-oriented research and the application of fundamental knowledge (patents, spin-offs, collaboration with industry).