PhD candidate 'Improving gene variant interpretation by transactivation and functional readout'

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PhD candidate 'Improving gene variant interpretation by transactivation and functional readout'

Apply

Your role

We are seeking a highly motivated PhD candidate to join our research team working at the intersection of genomics and rare diseases. The project focuses on the functional effects of diagnostic gene variants after activation of the normally silent genes in readily available tissue (blood/fibroblasts).

Whole genome sequencing (WGS) is standard of care in diagnostic testing for rare hereditary disorders. This results in the detection of more variants of unknown significance (VUS) outside the coding regions. To test whether VUS in intronic regions lead to a functional loss of a gene, analyses at the RNA level are required. Without the experimental proof of splicing defects, many of these variants will remain inconclusive. However, because many genes show little to no expression in easily accessible tissues such as blood, performing these tests is technically challenging. By transactivation assays these silent genes can be activated and RNA studies will be possible. Transactivation of these silent genes also facilitates the interpretation of missense variants of uncertain pathogenicity when a functional readout is available.

You will contribute to the validation of these variants by activating expression followed by transcript analyses (transcriptomics) and/or functional tests (cellular location, protein folding, enzyme activity, etc.). The work will involve close collaboration between clinicians, bioinformaticians, and molecular biologists in an interdisciplinary and translational research environment.

Tasks:

- Identifying eligible variants from a historic database

- Creating CASP9 based constructs for gene activation and transduction of patient cells

- Transcript and transcriptome analyses of the transduced cells

- Functional readouts of protein (immunohistochemistry, western blotting, enzymatic readouts)

- Present findings at local and (inter)national scientific meetings

- Writing scientific papers

- Work in an interdisciplinary team with other students and scientists to discuss, plan and perform research

- Finish the project with a scientific dissertation

Your workplace

The Department of Genetics is involved in genetic counseling, diagnostic and scientific research into genetic disorders, rare diseases and congenital abnormalities.

The department has over 400 employees and consists of three closely collaborating sections: Clinical Genetics, Genome Diagnostics, and Genome Research. This collaboration results in a leading department with a constant drive for innovation and improvement in diagnostics and genetic care.

The department of Human Genetics participates in several of the Radboudumc Research programs, such as the research program 'Genomics for Rare Diseases' and 'Hereditary Cancer'. These programs work at the forefront of rare disease gene and mechanism discoveries, aiming to enhance rare disease understanding and diagnostics through comprehensive data sharing, advanced genomic technologies, and functional interpretation of genetic variation. The research of this PhD trajectory is embedded within the Research Institute for Medical Innovation, and the development of the PhD candidate is supported by the Radboud Graduate School.

At the department of Human Genetics, you work on the diagnosis and treatment of hereditary disorders in patients and their families. You work in the outpatient clinic or in the laboratory for diagnostic testing, where genetic, metabolic, and neurochemical analyses are performed. In addition, you contribute to research exploring the relationship between genes and disease. As a leading, multidisciplinary department, you provide high quality genetic healthcare and contribute to scientific progress.

Your profile

Candidates must hold a Master's degree in Molecular Biology, Genetics, Medical Biology, Biomedical Sciences, or a related discipline. We are looking for an enthusiastic and motivated candidate with a strong and demonstrable interest in biology, genomics and rare diseases.

Experience with molecular biology is highly desirable.

The ideal candidate demonstrates:

- A critical and analytical scientific mindset

- Attention to detail and a structured approach to data management

- Excellent communication and interpersonal skills

- Fluency in both spoken and written English

- The ability to work independently as well as collaboratively in an interdisciplinary research team

- Curiosity, resilience, and a strong drive to learn and innovate

This position offers a dynamic and supportive research environment with ample opportunities for professional and academic development.

Good to know

  • The first job interviews will take place on May 6, 2026. Please take this into account.
  • This position requires a Certificate of Conduct (VOG).

We are recruiting for this position ourselves. Unsolicited marketing is not appreciated, but do feel free to share the vacancy in your network!

Want to know more?

We’re happy to provide more information!

Lisenka Vissers

Attractive employment conditions

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