The position

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.

Main tasks

· 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.

Your profile

MSCA eligibility

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.

Project-specific profile

· 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 events.

What we offer

A full-time employment contract for 36 months as a salaried researcher, with full social security coverage, under the rules of the Marie Skłodowska-Curie Actions. This is a paid employment contract, not a stipend or scholarship.

We offer you a temporary, full-time PhD-position for a total duration of 4 years (36 hours / 5 days a week) in our group. You will also collaborate with various research groups at the Princess Máxima Center and abroad. You will initially be contracted for a period of 1 year, with a possible extension. Your gross monthly salary will start in FWG 45-6 with a salary of €3.813,- gross a month for a fulltime working week (36 hours). You also receive 8.33% holiday allowance and 8.33 % end-of-year bonus. The Princess Máxima Center operates according to the collective labor agreement ‘CAO ziekenhuizen’.

Beyond salary, you will receive:

· Supervision by a world-leading, interdisciplinary supervisory team.

· A secondment of around three months with an ORFeus industry partner (Enara Bio).

· A structured training program: network-wide schools, transferable-skills training, workshops, and international conferences.

· Enrollment in a doctoral program leading to a PhD.

Duration and funding beyond the MSCA contract

The MSCA employment contract covers 36 months of full-time, fully funded employment. In line with the host institution's doctoral policy, the host funds completion of the doctorate beyond the 36-month MSCA contract as continued employment at the standard national doctoral salary scale; terms confirmed at offer stage.

Working at the Princess Máxima Center

The Princess Máxima Center for Pediatric Oncology in Utrecht is the largest childhood cancer center in Europe, uniting top-level care and research under one roof on the Utrecht Science Park. Its research institute offers a collaborative, international environment with state-of-the-art genomics, proteomics, and functional-genetics facilities.

You will join the group of Dr. Sebastiaan van Heesch, which studies the translatome and the non-canonical, dark proteome of cancer using ribosome profiling, proteogenomics, and mass spectrometry. You will work closely with the group of Prof. Reuven Agami at the Netherlands Cancer Institute, a pioneer of stress-induced amino acid substitutions in cancer. You will enroll as a PhD candidate at Utrecht University, most likely in the Cancer Stem cells & Developmental biology program.