RESOLUTE - Research Empowerment on Solute Carriers

RESOLUTE is a public-private partnership with 13 partners from academia and industry with an overarching goal: To trigger an escalation in the appreciation and intensity of research on solute carriers (SLCs) worldwide and to establish SLCs as a tractable target class for medical research and development.

RESOLUTE is funded by a grant from the Innovative Medicines Initiative (IMI) and is resolved to create a decisive advancement in the overall tractability of the Solute Carrier class of protein transporters (SLCs) by providing practical and conceptual advances, and making its research output available openly and pre-competitively to the scientific community. We argue that the ~400 members of this class represent a largely untapped source of new potential drug targets and thus merit the efficiency of scale that can be achieved only through systematic and coordinated efforts.

RESOLUTE's impact will transcend the funded consortium and funding period by providing the evidence for the feasibility of turning the SLC group of proteins into attractive drug targets. This will be achieved by empowering the community with reagents, research tools, protocols, and databases as well as the necessary ‘social and cultural’ instruments and exchange platforms. Thus, RESOLUTE will become an example of how a relatively understudied and biochemically demanding group of proteins can be ‘unlocked’ for research and development in a public-private partnership. Through the coupling of an inclusive, ‘open-access ethos’ to the 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 to the global benefit of basic academic research through to applied research in small biotech and pharmaceutical companies.

Solute Carriers

Solute carrier (SLC) membrane transport proteins control essential physiological functions, including nutrient uptake, ion transport, and waste removal. SLCs can be seen as gatekeepers and include over 400 membrane proteins arranged into 65 families based on sequence similarity. SLCs are the second-largest family of membrane proteins in the human genome.

SLCs are secondary active or facilitated transporters that translocate soluble molecules across cellular membranes. They can use ion gradients to drive uphill transports, work as exchangers, or facilitate passive diffusion of specific molecules. SLCs are vital for maintaining homeostasis in the body and in individual cells, and genetic polymorphisms in SLCs are associated with several diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and schizophrenia. Further- more, SLCs can function as drug targets, as well as constitute paths for drug absorption into specific organs.

Compared to other gene families of similar stature, SLCs are relatively understudied, with more than 30 % being orphan.

Consequently, the time is right for a systematic attack on SLC function, specificity, and regulation, taking into account kinship and expression, as well as the dependencies that arise from the common metabolic space.