PhD-student in cellular neuroscience

As a PhD student, you will be working on a project called "Disease mechanisms and intervention strategies for SNAREopathies". We use technology to produce human neurons and create human neuronal networks in vitro that severe mental disorders, such as the model SNAREopathies are a diverse group of brain disorders caused by mutations in eight genes that together drive the secretion of chemical signals in the brain. SNAREopathies are characterized by severe developmental delay, intellectual disability, motor problems and often epilepsy.

Currently we have no cure for these patients beyond seizure control. This project aims to characterize the cellular disease mechanisms for SNAREopathies, especially for the most prevalent group (mutations in STXBP1), and to design intervention strategies.

Our research is developed within the framework of a European consortium, ESCO, where scientists, clinicians, patient families and industrial partners work together to promote research, therapy development and trial readiness for STXBP1-related disorders.

Within this framework, you will work together in a team of basic scientists, building on previous studies in the department that have established genomic, proteomic and cellular changes in SNAREopathy cell models, in induced pluripotent stem cell (iPSC)-derived neurons from SNAREopathy patients.

The key objectives for this project are:

1. To upscale and multiplex assays to quantify STXBP1 mRNA and analyze the regulation of STXBP1 expression.
2. To test candidate intervention strategies that upregulate STXBP1 expression.
3. To establish cellular phenotypes in patient-derived neurons that generalize over different patients.
4. To test candidate intervention strategies that normalize these phenotypes. In addition to these core activities, you will perform bioinformatic analyses using your own data and large public data resources and integrate your findings with clinical data (symptoms, EEG, etc).

Finally, you will contribute to other activities of the STXBP1 team, including interactions with clinicians and patient families, supervising BSc/MSc students during internships, contribute to teaching activities (10%), organizing outreach activities, and organizing and participating in international meetings.

The department also performs collaborative research with large biotech/pharma companies on SNAREopathies and new therapeutic strategies will be developed together with these and our own spin out company Neurospector. All the methodology, cell models, equipment, analysis software and viral vectors are available from the start of the projects.

You hold or will soon obtain a master’s degree in (Bio)physics, (Bio)chemistry or (Medical) Biology, preferably with hands-on experience in cellular research, and a strong motivation to pursue a career in science. The ideal candidate would have:

• An eye for detail.
• Previous lab experience: Hands-on experience in laboratory techniques builds confidence and competence, allowing for efficient execution of experiments and quicker troubleshooting.
• The ability to critically analyze scientific literature. This skill enables you to identify gaps in knowledge, design relevant experiments, and stay informed about advances that could influence your research direction.
• Interest and understanding of current research trends in neuroscience. Being up to date with the latest findings and technologies helps position your work within the broader scientific context and drives innovative approaches.
• Persistence in the face of experimental setbacks. Research often involves trial and error; resilience is essential to push through challenges and maintain motivation toward meaningful discoveries.