About
We can read genomes with ease, yet a whole layer of biology has stayed in the dark. ORFeus exists to bring it to light, and to train the scientists who will.
A paradox at the heart of modern biology
The dark proteome, the thousands of microproteins our standard methods have missed, is one of the largest remaining blind spots in biology. For years these proteins fell below the resolution of the instruments and the thresholds of the software. That is changing fast. New techniques in ribosome profiling, proteomics and AI are making it possible to detect what the genome really translates. The first microprotein-based drug has reached clinical trials. Funders, including the Cancer Research UK Grand Challenges, have named the dark proteome a strategic priority. But the field still rests on a handful of specialized, often disconnected teams, with few shared tools and almost no researchers trained across the full range of methods it demands.
From paradox to paradigm
ORFeus exists to close that gap. The network builds the methods and reference data to detect what the genome truly translates, works out what these microproteins do, and tests where they matter most, in cancer and the immune system. The field needs shared, standardized tools and a generation of scientists fluent in more than one discipline. ORFeus is designed to deliver both, and to make the study of the dark proteome an established part of biology rather than a puzzle at its edge.
Why it matters
Microproteins were overlooked for a long time, but more and more of them are turning out to have specific roles in the cell, in metabolism, development, immune regulation and the response to stress. What matters most for ORFeus is what they mean for disease. Some microproteins appear mainly in cancerous or stressed cells. Some are displayed on the cell surface, where the immune system can encounter them. Others seem to fine-tune signalling pathways that go wrong in a range of conditions. Taken together, they represent a large, mostly untapped layer of biology with real relevance for diagnostics, drug development and how we understand disease at the molecular level. Much of this is still early, and testing which leads are real is exactly what ORFeus is for.
Why this consortium
No single lab, and no single discipline, can map the dark proteome. It takes ribosome profiling, mass spectrometry, proteogenomics, structural biology, evolutionary genomics and AI, working on shared questions and shared data. It also takes a new kind of scientist, fluent across all of them. A Marie Skłodowska-Curie Doctoral Network is built for exactly this.
ORFeus unites 15 of Europe’s leading research groups, 11 industry and research partners and 15 international advisers around one mission, and trains 15 doctoral researchers across all of them at once. The consortium brings together the teams that produced many of the field’s foundational methods and datasets, including the first standardized annotation framework for translated ORFs and the first consensus landscape of protein-level evidence for microproteins. Its industry partners, from Oxford Nanopore Technologies and Bruker to Tesorai and Enara Bio, span the full innovation pipeline from sequencing and mass spectrometry to drug development. The work supports major European goals in genomics, the fight against cancer, and personalized medicine. The result is science no partner could do alone, and a generation of researchers ready to lead a new field.
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Funded by the European Union
Marie Skłodowska-Curie Actions Doctoral Network under Horizon Europe. Grant Agreement No. 101309891.
Project record on CORDIS