Date: 06.11.2025
3Stops2Go all the way!
Imagine a crossroad with traffic lights and cars driving up and down intersecting streets. Drivers leave their fingerprints on the steering wheel as they navigate through their lives. Indeed, each of us has unique fingerprints, and each of us is sometimes driving through a wave of green light before having to stop at red due to various obstacles. But only some of us are stopping and not running most of the time. We are talking about people suffering from monogenic diseases. Their health conditions are severe, yet the underlying genetic problem is often very simple. With 3Stops2Go, four researchers - Leos Valasek and Julius Lukes from Czech Republic, Olivier Namy from France, and Mark Osborn from the USA - have teamed up to form an initiative aiming to ameliorate the number of red lights these people face daily!
Fig. above: Synergy of brains and wet labs across the ocean.
These diseases include Cystic fibrosis (CS), Fanconi anemia (FA), Hurler syndrome (MPS-IH), Duchenne muscular dystrophy (DMD), Epidermolysis Bullosa (EB), etc. The common denominator of all of them is a specific type of mutation, known as a premature termination codon (PTC). PTCs cause early termination of protein synthesis of essential human genes, leading to truncated, non-functional proteins. They are responsible for approximately 11% of genetic diseases in general.
The 3Stops2Go grant recipients found their main inspiration in nature when they discovered specific species among single-celled organisms called protists, which have alternative genetic codes and can carry many PTCs in their genes while remaining fully viable. This is due to a specifically altered structure of small RNA molecules called tRNAs, which are essential for protein synthesis. Based on these findings, they plan to develop specific tRNAs and other tools to bypass genetic errors in organisms with common genetic codes, such as humans. They then intend to examine these tools on monogenic PTC disease cells derived directly from children’s patients suffering from these diseases and on a mice model with PTC causing Hurler syndrome. The long-term vision, extending beyond the scope of this research initiative, is to leverage these tools to pave the way for clinical applications (Fig. 1).
Each of the 3Stops2Go grantees is an expert in a different field, such as protist biology, tRNA biology, protein synthesis, disease pathology, gene therapy, and drug development. Therefore, to achieve this ambitious goal, they have synergized to create an international and interdisciplinary team that transcends Trump (former Atlantic) ocean boundaries
From Protozoa to Patients – Working Scheme of the 3Stops2Go Project
Project ERC Synergy: Three stop codons to get over to flourish (3Stops2Go)
Researchers:
Leoš Valášek, Institute of Microbiology, Czech Academy of Sciences, Czech Republic
Julius Lukeš, Biology Centre, Czech Academy of Sciences, Czech Republic
Olivier Namy, Université Paris-Saclay, CEA, CNRS, France
Mark Osborn, University of Minnesota, USA
ERC funding: €9.8 million over 72 months
