Neuropeptides are by far the largest group of chemical signals in the brain, playing a vital role in a wide range of brain functions, from sleep to cognition. Yet, the way these signals are produced, packaged, transported, and secreted by brain cells is still poorly understood. Furthermore, dysregulation of neuropeptide signaling is implicated in numerous brain disorders (e.g., autism, mental retardation) and neuropeptides are used treatment for many of these, including epilepsy. Neurons secrete neuropeptides from dense core vesicles (DCVs). The aim of this project is to unravel the mechanisms of DCV trafficking and secretion in neurons, from their biogenesis in the soma to their fusion at synapses. This project utilizes human iPSC-derived neurons and genetically encoded reporters of DCV trafficking and fusion. Using CRISPR/Cas9 gene editing, we have generated mutations in a collection of candidate genes, including mutations associated with human brain disorders. Additionally, human patient samples have been obtained to generate human neuron models for analysis in this project. This project will use life cell imaging to analyse DCV trafficking and secretion in these human models, building on the previous establishment of detection of DCV secretion in living neurons with single vesicle resolution and characterized several molecular factors that regulate secretion. In this project we will exploit these tools and methods to gain deeper understanding of the secretory pathway and its dysregulation in disease.

You will be part of international research networks and exploit a variety of other analysis tools available here. You will be appointed in Amsterdam and work primarily in Amsterdam with regular visits to the other labs. The PhD-students will be trained on site. All the methodology, equipment, analysis software and viral vectors are available from the start of the project.

We are looking for a student with the following qualifications

• a master degree in biomedical sciences or biophysics with neuroscience specialization
• hand-on experience with molecular and cellular neuroscience, especially the methods listed above
• hands-on experience with bioinformatics is an advantage
• a strong motivation to pursue a career in science.

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 (PhD) per month during the first year and increases to €3,247 (PhD) per month during the fourth year, based on a full-time employment. The job profile: is based on the university job ranking system and is vacant for at least 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:

• 8% holiday allowance and 8.3% end-of-year bonus
• contribution to commuting expenses
• optional model for designing a personalized benefits package

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
The Faculty of Science inspires researchers and students to find sustainable solutions for complex societal issues. From forest fires to big data, from obesity to medicines and from molecules to the moon: our teaching and research programmes cover the full spectrum of the natural sciences. We share knowledge and experience with leading research institutes and industries, both here in the Netherlands and abroad.

Working at the Faculty of Science means working with students, PhD candidates and researchers, all with a clear focus on their field and a broad view of the world. We employ more than 1,250 staff members, and we are home to more than 11,000 students.

About the department, institute, project
The CNCR in Amsterdam (see www.cncr.nl) participates in the Graduate School ONWAR (www.ONWAR.nl). This position is in the Department of Functional Genomics and the project is: Mechanisms of neuropeptide signalling in human brain