About the Project
Use evolution, human genetic variation and CRISPR screens to find out which hidden proteins are functional, at the Hospital del Mar Research Institute in Barcelona.
Why it matters
Thousands of microproteins are now being found, many of them recently evolved. Which of them actually do something in the cell is largely unknown. Evolutionary signals, such as how strongly a sequence is conserved across species or constrained within human populations, are one of the few ways to tell a functional microprotein from a translation product with no function.
The project
You will build computational models that predict which microproteins are functional by combining ribosome profiling data, phylostratigraphy (estimating a gene's evolutionary age) and human genetic variant data from gnomAD and the UK Biobank. You will then test your best predictions with CRISPR-Cas9 screens in cancer cell lines, looking at cell growth, drug resistance and DNA repair. Your constraint data feeds the network's AI prediction models, and validated microproteins go on to the cancer projects in the network.
What you will do
- Build models that integrate ribosome profiling, evolutionary age and population genetic constraint
- Prioritize candidate microproteins for validation
- Run CRISPR-Cas9 functional screens in cancer cell lines
- Share software and datasets on the ORFeome platform
About ORFeus
This PhD is one of 15 in ORFeus, a Marie Skłodowska-Curie Actions Doctoral Network funded by Horizon Europe. ORFeus brings together 15 research groups in eight European countries, with industry and research partners, to study the dark proteome: the many microproteins made from small open reading frames long dismissed as non-coding. Together, the 15 projects aim to find these proteins, understand what they do, and test their potential in diagnosis, immunotherapy and drug development, with a strong focus on cancer.
Where you will work
You will join the group of Prof. M. Mar Albà at the Hospital del Mar Research Institute in Barcelona, part of the CERCA network of Catalan research centers. The group studies how new genes emerge in evolution and how microproteins are expressed in cancer. You will work closely with the group of Prof. Simon Elsässer at the University of Freiburg, which brings experimental and proteomics expertise.
Who should apply
We welcome applications from bioinformaticians, computational biologists and evolutionary geneticists who also want hands-on experience with CRISPR screens. The project is mainly computational, with experimental validation.
- A master's degree (or equivalent) in bioinformatics, computational biology, evolutionary genomics, genetics, molecular biology, or a related field
- Strong programming and data-analysis skills (for example Python or R)
- Good written and spoken English
- Nice to have: comparative or evolutionary genomics, ribosome profiling or NGS data, gnomAD or UK Biobank data, CRISPR-Cas9 screening
Eligibility (MSCA rules)
Living or studying in the UK? You are likely eligible for this position.
You must not have lived or carried out your main activity (work, studies) in Spain for more than 12 months in the 36 months before your start date. Compulsory national service, short stays such as holidays, and time spent in a refugee status procedure do not count. You must not hold a doctoral degree. Any nationality may apply.
What we offer
- A 36-month, full-time employment contract with full social security, under MSCA rules
- Supervision by Prof. M. Mar Albà and Prof. Simon Elsässer, with mentoring from partners across academia and industry
- A secondment of around three months with an ORFeus industry partner
- Training with 14 other ORFeus PhD candidates across Europe: network schools, workshops, transferable skills and international conferences
- PhD enrollment at Universitat Pompeu Fabra
Practical details
Start around March 2027; the exact date depends on the host institution. Reference letters are requested only at the interview stage.
How to apply
You can only apply via https://www.orfeus-dn.eu/apply/ - registering your interest on this website is not equivalent to an application. You can apply to up to three of the 15 ORFeus projects and rank them; every project you rank considers you. The application asks for:
- a few eligibility questions
- a short motivation per project (150 to 200 words)
- your experience with the project's key techniques
- your CV
- an overview of your bachelor's and master's grades, in one PDF
- contact details for two referees
- a short motivational video
Funding Notes
Fully funded 36-month employment contract in ORFeus, an MSCA Doctoral Network (Horizon Europe, GA 101309891), with full social security. A salary, not a stipend. Salary details for this position are on the application page. Open to all nationalities, including applicants living or studying in the UK. Mobility rule: you must not have lived, worked or studied in Spain for more than 12 months in the 36 months before your start date. Applicants must not hold a doctoral degree.