ORFeus doctoral network
Project 11: Non-canonical translation from smORFs in HPV-driven cancer (Nicola Ternette)
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HPV-driven Cancers Research Fellow
Project Overview
HPV-driven cancers arise when human papillomavirus integrates into the host genome, and this integration can generate viral-human hybrid transcripts. Non-canonical open reading frames and small open reading frames (smORFs) within these transcripts may be translated into peptides that standard protein catalogues miss, yet whether such peptides are presented to the immune system and can be recognized by T cells in HPV-driven tumors remains largely unmapped.
This project will map the translation of non-canonical ORFs from viral, and viral-human hybrid transcripts and interrogate their contribution to tumor-immune recognition in HPV-driven cancers, combining long- and short-read RNA sequencing, ribosome profiling, proteomics, and immunopeptidomics in cell lines and primary human tumors to build the 'HPV Immune Map' and assess the immunogenicity of the peptides it identifies. It sits within ORFeus Work Package 3, which investigates the therapeutic and diagnostic relevance of the dark proteome in cancer and immunology, and anchors the antigen-discovery arm of the work package, linking to partner projects on cryptic peptide presentation, antigen-presentation regulation, and rare translation events.
Main Tasks
- Characterize viral-human hybrid transcripts in reference HPV cell lines and head and neck squamous cell carcinoma (HNSCC) tumor cell lines using long- and short-read RNA sequencing and ribosome profiling.
- Identify and validate smORF-derived peptides from these transcripts using proteomics and immunopeptidomics in cell lines and in up to 30 primary human tumors, cross-validating rare translation events against the large-scale catalog built by other doctoral candidates (DCs) in the network, here DC3.
- Assess the immunogenicity of the identified peptides by characterizing T-cell responses and building the 'HPV Immune Map', interpreting the results alongside the antigen-presentation insights of DC14 and contributing candidate peptides to the prediction work of DC15.
- Collaborate across the ORFeus network, contribute data and validated peptide sets to the shared ORFeome platform, and produce the project's scientific report.
Methods and Platforms
- Long- and short-read RNA sequencing
- Ribosome profiling (Ribo-seq)
- Mass-spectrometry-based proteomics and immunopeptidomics
- HLA multimer technology for T-cell detection
- Functional immunogenicity assays in cell lines and primary human tumors
- Contributing data to the ORFeome platform
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Secondment
You will spend around three months at Immudex (Copenhagen, Denmark), mastering HLA multimer technology to detect low-frequency T cells that recognize non-canonical peptides. You will also be guided by an independent academic advisor, with the possibility of a short, primarily virtual research exchange to strengthen 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 United Kingdom 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 University of Dundee.
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 bachelor's degree (or equivalent) in molecular biology, immunology, cancer biology, biochemistry, biotechnology, bioinformatics, or a related life-science field.
- Hands-on laboratory experience with cell culture and molecular biology, and familiarity with mass spectrometry, proteomics, or immunology techniques.
- Desirable: experience with immunopeptidomics, HLA biology or T-cell assays, ribosome profiling or RNA sequencing, analysis of proteomics or multi-omics data, and an interest in cancer antigens, microproteins, and the dark proteome.
- Good 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.
- A full-time position as a doctoral fellow, consisting of an initial period of 12 months, which, after a positive evaluation, will be extended to a total maximum of 48 months.
- The individual fellowship amount is determined by the University of Dundee HR team based on family status and seniority and is currently estimated at up to approximately £61,081 per annum. The final salary and associated employment costs will be determined by the University in accordance with the applicable fellowship conditions and UK tax, National Insurance and pension requirements.
- The position is funded within the Marie Skłodowska-Curie Actions Doctoral Network (MSCA-DN) ORFeus. Applicable MSCA-DN mobility and family allowances will be handled in accordance with the MSCA-DN and University of Dundee regulations.
- Beyond salary, you will receive:
- Supervision by a world-leading, interdisciplinary supervisory team.
- A secondment of around three months with an ORFeus industry partner (Immudex).
- A structured training program: network-wide schools, transferable-skills training, workshops, and international conferences.
- Enrollment in a doctoral program leading to a PhD.
- 30 days annual leave allowance including University closure days.
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Working at the University of Dundee
The project is based at the Faculty of Life Sciences at the University of Dundee; a world-class academic institution with a reputation for the excellence of its research, its high-quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 40 countries worldwide the Faculty provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.
You will join the group of Prof. Nicola Ternette, which specializes in immunopeptidomics and the discovery of tumor antigens presented on HLA molecules, including antigens from HPV-driven cancers. You will work closely with the group of Dr. Sebastiaan van Heesch at the Princess Máxima Center, who brings complementary expertise in microprotein biology and non-canonical ORF translation. You will enroll as a PhD candidate at the University of Dundee.
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