All life depends on the ability of cells to exchange substances with their environment. Nutrients, ions, and vitamins must be absorbed, while waste and special metabolites must be expelled. This fundamental process relies on transporter proteins embedded in cell membranes. Despite their crucial role, the function of many of the hundreds of human transporter-encoding genes has remained a mystery, slowing progress in fields ranging from cancer therapy to metabolic and neurological disease research.
Recognizing this challenge, the Superti-Furga group at CeMM first called for intensified research in a landmark 2015 article in Cell. Ten years later, CeMM and an international consortium have succeeded: by focusing on the largest family of transporters — the solute carriers (SLCs) — they have more than doubled existing knowledge and laid the foundations for future breakthroughs in understanding and targeting these critical proteins.
A Megaproject on Membrane Transporters
In a massive, coordinated effort, 120 researchers from 13 institutions across eight countries came together under the RESOLUTE consortium. After more than five years of laboratory work, most of the experimental data were gathered. The CeMM team, supported by a few key partners and primarily financed by the Austrian Academy of Sciences, then spent an additional year harmonizing, integrating, and interpreting the extensive datasets.
The result is a transformative expansion of the known biology of SLC transporters, integrating multidisciplinary experimental and computational approaches. Their findings illuminate the intricate logistics of chemical traffic within human cells, offering powerful new resources for the scientific and medical communities worldwide.
"It is difficult to find in history a comparably ample and strong ‘push’ of enabling knowledge and tools towards an individual target class, so heavily involved in human disease," says Giulio Superti-Furga, Scientific Director of CeMM and Coordinator of the RESOLUTE consortium. "With these four studies, we hope to have lowered the barrier for transporter research and catalyzed a surge in biomedical discovery for years to come."
The effort not only generated vast scientific insights but also produced an impressive arsenal of reagents, datasets, and analytical tools — all made freely available to the global scientific community via https://re-solute.eu.
"What is the most important outcome is that we were able to annotate most, if not all, solute carriers with functional information and have created a vast arsenal of tools that now serve the global research community. This achievement, culminating in the RESOLUTE knowledge base, represents a unique resource and a true community treasure," says Ulrich Goldmann, a key researcher responsible for data integration.
Giulio Superti-Furga adds: "We are deeply grateful for the support of the Innovative Health Initiative, IHI, (previously Innovative Medicines Initiative, IMI), a partnership of the European Federation of Pharmaceutical Industries and Associations, EFPIA, and the European Union, EU, and the contributions of all our outstanding partners—without whom this project would never have come to life. Since a couple of years, CeMM has shouldered much of the responsibility to validate, annotate, maintain and further develop this invaluable platform. Looking ahead, there is a genuine opportunity for funding bodies and industry stakeholders to help secure the long-term sustainability and expansion of this effort. It is not too late to propose and contribute the means to ensure this community treasure continues to grow and inspire biomedical research worldwide."
Project Manager Tabea Wiedmer, who took over after the premature and tragic death of Daniel Lackner, emphasizes the collaborative spirit of the initiative: “Coordinating the research efforts of such a large group of scientists was a formidable challenge, especially during COVID. We had to develop all sorts of creative strategies to keep partners focused and motivated — but it worked wonderfully. The success relies heavily on efficiently combining expertise across fields.”
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Funding: This major initiative was funded by the Innovative Medicines Initiative 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Additional support was provided by the Austrian Academy of Sciences and participating institutions.
The four studies were published online ahead of print in Molecular Systems Biology on May 12, 2025: 1)DOI: 10.1038/s44320-025-00106-4 2)DOI: 10.1038/s44320-025-00109-1 3)DOI: 10.1038/s44320-025-00105-5 4)DOI: 10.1038/s44320-025-00108-2