Solute carrier transporters (SLCs) are proteins located in cellular membranes and function as cellular gates that control nutrient uptake, ion transport and waste removal. They constitute the largest family of molecular transporters with more than 400 members which are arranged into 71 sub-families. SLCs play critical roles in metabolism and immunity as they are responsible of maintaining cellular homeostasis. They also play an integral role in drug absorption into specific organs and genetic variants of SLCs are associated with several human diseases, such as autism, Alzheimer's disease, schizophrenia, diabetes, metabolic and cardiovascular diseases, and several types of cancer, hence SLCs constitute emerging therapeutic targets. Despite their physiological and medical relevance, a large proportion of SLCs can still be considered ‘orphans’ in terms of substrate specificity or function (Meixner et al., Molecular Systems Biology, 2020).
RESOLUTE – Research Empowerment on Solute Carriers
RESOLUTE is a private-public partnership coordinated and led by Giulio Superti-Furga (CeMM) and Claire Steppan (Pfizer). RESOLUTE is formed by 6 partners from academia, 6 partners from the pharmaceutical industry and 1 partner which is a small and medium enterprise (SME). The project started in July 2018 and with a duration of 5 years, RESOLUTE is funded by the Innovative Medicines Initiative (IMI), the EU and the EFPIA (European Federation of Pharmaceutical Industries and Associations). The mission of RESOLUTE is to intensify research on SLCs worldwide and to establish SLCs as a novel target class for medical research (Superti-Furga et al., Nature Reviews Drug Discovery, 2020).
Through the coupling of an open-access ethos to our results, techniques and reagents with the highest-possible quality of research output, RESOLUTE expects to accelerate the pace of research in the field of SLCs. This will create a global benefit for both basic academic research as well as the applied research in biotech and pharmaceutical companies. Hundreds of laboratories have already found access to our collections.
REsolution – Medical Genetic Solutions for RESOLUTE
The REsolution consortium focuses on human genetic variations in transporters and their link to disease. REsolution is a public-private research partnership coordinated and led by Giulio Superti-Furga (CeMM) and Claire Steppan (Pfizer). It consists of 6 partners from academia, 2 partners from the pharmaceutical industry and 1 SME. It started in June 2021 and with a duration of 2 years, REsolution is supported by the IMI, the EU and the EFPIA.
REsolution exploits the unique opportunity to link the RESOLUTE knowledge to physiology and disease through human genetics and has the following objectives:
To assemble human SLC genetic information for the entire family and annotate within the RESOLUTE knowledgebase
To study the structure-activity relationship (SAR) for selected SLC variants
To use deep mutagenesis and artificial intelligence to develop the equivalent of a “Rosetta stone” allowing the interpretation of SLC genetic variation
This will allow to not only contextualize SLCs in the current human medical genetics landscape, but also to create an SLC prioritization rationale and a resource of the whole SLC family for the pharmaceutical industry valid for years to come, envisioned as the SLC compendium. The goal is to maximize the chances that SLC transporters will become successful drug targets and use the growing amount of data becoming available on genetic variations and disease association to assign pathophysiological relevance to individual transporters.