Project dark proteome and non-canonical translation in cancer; Sebastiaan van

This PhD is hosted in the group of Sebastiaan van Heesch at the Princess Máxima Center, with Reuven Agami (Netherlands Cancer Institute) as co-supervisor, and is carried out within the ORFeus network. The project studies the dark proteome in cancer: the proteins and peptides made from stretches of the genome long considered non-coding, produced through non-canonical translation when cells read the genetic code in unexpected ways.

A central question is how cells switch on this hidden layer of coding and what it means mechanistically for cancer, with particular interest in how it unfolds under the kind of cellular stress that is typical of a tumor cell and its environment.

The project runs in parallel to ILLUMINE, the Cancer Grand Challenges project on the dark proteome, and will integrate and collaborate with it where the science aligns. ILLUMINE aims to map and characterize the dark proteome, reveal its role in cancer, and uncover novel, potentially universal tumor antigens and new immunotherapies for hard-to-treat cancers.

The precise focus will be shaped together with the successful candidate and the supervisory team, drawing on ribosome profiling, proteomics, and immunopeptidomics alongside computational analysis.

• Apply and develop approaches in ribosome profiling, proteomics, and immunopeptidomics to study non-canonical translation and the dark proteome.
• Integrate experimental and computational analyses to interpret the results.
• Collaborate across the ORFeus network, contribute data to the shared ORFeome platform, and produce the project's scientific report.

Methods and platforms: ribosome profiling (Ribo-seq), mass-spectrometry proteomics and immunopeptidomics, and computational analysis.

Secondment: you will spend around three months at Enara Bio (Oxford, UK), integrating your findings into neoepitope prediction workflows and validating the immunogenicity of top candidates. You will also be guided by an independent academic advisor, with the possibility of a short, primarily virtual research exchange to strengthen the computational side of the project.

You must meet all of the following on your recruitment date:

• You do not already hold a doctoral degree. If you have defended a doctoral thesis but the degree has not yet been formally awarded, you are not eligible.
• Mobility rule: you must not have lived or carried out your main activity (work, studies, and so on) in the Netherlands for more than 12 months in the 36 months immediately before your recruitment date. Compulsory national service, short stays such as holidays, and time spent in a procedure to obtain refugee status under the Geneva Convention do not count toward the 12 months.
• You hold, or will hold before the start date, a degree that formally entitles you to enroll in a doctorate, and you can enroll in the doctoral program at the Princess Máxima Center / Utrecht University.
• Candidates of any nationality may apply. There is no limit on prior research experience, as long as you do not already hold a doctorate.

• A master's degree (or equivalent) in molecular biology, biochemistry, biomedical sciences, bioinformatics, immunology, or a related field.
• Hands-on experience in at least one of: ribosome profiling or next-generation sequencing, mass-spectrometry proteomics or immunopeptidomics, or the molecular and cell biology of cancer.
• Desirable: programming and bioinformatics for omics data (for example Python or R); experience with HLA/immunopeptidomics, CRISPR, or cell culture; interest in tumor immunology.
• Excellent written and spoken English.
• Motivation for interdisciplinary, collaborative research, and willingness to travel for the secondment and network…