The position

Only a fraction of the genome codes for the proteins in standard reference catalogs. Many small open reading frames (smORFs) are translated into microproteins that those catalogs miss, but which of these recently evolved microproteins actually carry out a biological function remains largely unknown. Evolutionary signatures, such as how strongly a sequence is conserved or constrained across species and within human populations, offer one of the few ways to tell a functional microprotein from a spurious translation product.

This project will build and validate computational models that predict the functionality of recently evolved microproteins from evolutionary features, integrating ribosome profiling data, phylostratigraphy (evolutionary age), and genetic variant data from public resources such as gnomAD and UK Biobank. It sits within ORFeus Work Package 2, which moves from discovery to function, and provides an evolutionary framework for the wider network: shared variant and DepMap data from partner projects help measure sequence constraints, the resulting constraint data feeds back into the network's AI prediction models for validation, and top candidates are tested in CRISPR-Cas9 screens in cancer cell lines, with phenotypic hits connecting to partner work on cancer.

Main tasks

● Develop computational models that predict microprotein functionality by integrating ribosome profiling data, phylostratigraphy (evolutionary age estimates), and genetic constraint data from public resources such as gnomAD and UK Biobank, drawing on shared variant and DepMap datasets from another doctoral candidate (DC) in the network, here DC12, to measure sequence constraints.

● Prioritize candidate microproteins for functional validation, with the resulting evolutionary constraint data contributing to the AI model validation carried out in DC1.

● Validate model predictions using CRISPR-Cas9 functional screens in cancer cell lines, assessing effects on cell growth, drug resistance, and DNA repair, with phenotypic hits informing the cancer work in DC13.

● Collaborate across the ORFeus network, contribute the validated software and datasets to the shared ORFeome platform, and produce the project's scientific report.

Methods and platforms: comparative and evolutionary genomics (sequence conservation, phylostratigraphy, and constraint analysis), ribosome profiling (Ribo-seq) data analysis, integration of population genetic variant data (gnomAD, UK Biobank) and DepMap datasets, CRISPR-Cas9 functional screens in cancer cell lines, and predictive software development, working with public and consortium datasets via the ORFeome platform.

Secondment: you will spend around three months at an ORFeus industry partner, applying the computational models to prioritize microproteins for therapeutic applications. 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 Spain 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 Hospital del Mar Research Institute / Universitat Pompeu Fabra (UPF).

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 bioinformatics, computational biology, genetics or a related quantitative or life-science field.

● Strong programming and data-analysis skills (for example Python or R) and an interest in evolutionary genomics and the analysis of large biological datasets.

● Desirable: experience with comparative or evolutionary genomics, ribosome profiling or next-generation sequencing data, population genetic variant data (for example gnomAD or UK Biobank), CRISPR-Cas9 functional screening, and an interest in 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. This is a paid employment contract, not a stipend or scholarship.

The salary has a living allowance and a mobility allowance, plus a family allowance if you have family obligations when you are recruited. The indicative gross salary for this position is 2,749.48 euros per month (plus 509.22 euros mobility allowance, and 473.36 family allowance if eligible). This is what you are paid before income tax and your own social-security contributions are deducted.

Beyond salary, you will receive:

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

● A secondment of around three months with an ORFeus industry partner.

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

● Enrollment in a doctoral program leading to a PhD.

● Paid leave

Working at the Hospital del Mar Research Institute

The Hospital del Mar Research Institute (HMRIB) is a biomedical research institute in Barcelona, Spain, and part of the CERCA network of Catalan research centers, with research spanning cancer, genomics, evolutionary biology, and computational biology.

You will join the group of Prof. Mar Albà, which studies the evolutionary emergence of new genes and the expression of microproteins in cancer using comparative genomics. You will work closely with the group of Prof. Simon Elsässer at the University of Freiburg, who brings complementary expertise in experimental biology and proteomics. You will enroll as a PhD candidate at Universitat Pompeu Fabra (UPF), the degree-awarding partner of the Hospital del Mar Research Institute.