Unravelling the mysteries of chemical transport across cell membranes
A coordinated international effort to shed light on how chemical substances are transported across cell membranes has resulted in four pioneering studies published in the journal ‘Molecular Systems Biology’. Supported by the EU-funded projects ReSOLUTE(opens in new window), EUbOPEN(opens in new window), REsolution(opens in new window) and GlyCANswer, the studies provide the first comprehensive blueprint of chemical transport pathways in human cells. Cells absorb nutrients, ions and vitamins and remove waste, a process that enables us to stay alive. This crucial process would not be possible without transporter proteins found in our cell membranes. However, scientists know very little about transporter-encoding genes, which has impeded progress in fields ranging from cancer therapy to metabolic and neurological disease research. By focusing on the largest family of transporters, the solute carriers (SLCs), the four studies cast valuable light on the intricate logistics of chemical traffic within human cells, more than doubling current knowledge of SLC transporters. Their findings are paving the way for future breakthroughs in medical applications involving these proteins. “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,” remarks the studies’ senior author Giulio Superti-Furga in a ‘EurekAlert!’ news release(opens in new window). “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,” adds Superti-Furga, who is scientific director at CeMM Research Center for Molecular Medicine (Austria), the project coordinator of ReSOLUTE and REsolution. Besides the extensive scientific insights on SLCs(opens in new window), the research has also led to a wide range of reagents, datasets and analytical tools(opens in new window) all freely accessible through the RESOLUTE website. “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,” notes CeMM researcher Ulrich Goldmann. “This achievement, culminating in the RESOLUTE knowledge base, represents a unique resource and a true community treasure.”
Four studies at a glance
The first(opens in new window) of the four studies focused on the metabolic mapping of the human SLC superfamily. Hundreds of SLC genes were systematically knocked out or overexpressed in human cell lines, revealing distinct metabolic and gene expression signatures and identifying potential substrates for 71 previously uncharacterised transporters. The second study(opens in new window) describes the development of a comprehensive, richly annotated and freely accessible database that charts the biochemical and biological properties of the SLC transporter family. The third study(opens in new window) discusses the complete SLC superfamily interactome. In this study, researchers mapped protein-protein interactions for nearly 400 SLCs, uncovering thousands of new connections and shedding light on fundamental regulatory mechanisms. The final study(opens in new window) provides the first genetic interaction map of SLCs. ReSOLUTE, EUbOPEN and REsolution have been supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry. The ReSOLUTE (Research empowerment on solute carriers (ReSOLUTE)), GlyCANswer (Decoding the Cancer Glycoproteome Driven Immune Response) and REsolution (Add medical genetic solutions to RESOLUTE (REsolution)) projects have ended. EUbOPEN (EUbOPEN: Enabling and Unlocking biology in the OPEN) ends in October 2025. For more information, please see: ReSOLUTE project website(opens in new window) EUbOPEN project website(opens in new window) GlyCANswer project REsolution project web page(opens in new window)