Transport proteins are the gate-keepers of our cells, effectively controlling the flow of nutrients and other molecules across the cell membrane. With over 400 members, solute carriers represent the largest class of transport proteins. Yet although they have been implicated in diseases ranging from Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) to schizophrenia, solute carriers have never been studied in detail.
The ReSOLUTE project aims to change that, by intensifying research in, and advancing our knowledge of, the solute carrier family. Specifically, the project partners plan to deliver practical research tools, protocols, databases and platforms on solute carriers. The project’s open access ethos means the results will be of benefit to researchers in universities as well as small and large biotech companies worldwide. Ultimately, the project results will aid in the identification of solute carriers that could be used as either drug targets or as pathways for enabling the transport of medicines into specific tissues.
Achievements & News
Solute carriers (SLCs) are proteins that bring nutrients and other substances across cell membranes. Any problems with how these proteins function can cause disease, and they are increasingly being considered as drug targets. Antibodies are powerful biological tools that can be used to study the function of SLCs, but despite the large number of commercial antibodies available to buy, the RESOLUTE team found that 80% don’t work against their purported target.###
‘What we can do now is to raise awareness in the scientific community and antibody vendors. We need to work together to develop better tools. By recognising this need, we can then work on a solution,’ said RESOLUTE communications manager Álvaro Inglés-Prieto in an interview with the IMI Programme Office.
‘We currently generate material and protocols and will share them with the community. This effort still remains a great challenge, but we think we are on a good track and the first results indicate that our approaches are successful.’
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IMI’s ReSOLUTE project has made the DNA reagents for 446 solute carriers freely available in the hope that the proteins might be used as targets in drug development. Solute carriers are bound to the cellular membrane and transport nutrients, like vitamins, sugars, and drugs. ###However, despite being the second biggest family of membrane proteins in the human genome, and despite being implicated in diseases, such as schizophrenia, ALS, Alzheimer’s, diabetes and cancer, there is still a great deal that we do not know about them. One of the objectives of the ReSOLUTE project is to generate reagents that would allow the scientific community to work more efficiently with this family of proteins and, hopefully, make use of them as targets for drug development.
‘Now, the consortium has made available the DNA sequence of approximately 400 solute carriers. The DNA has been codon-optimised, which basically means to improve the sequence to make it easier for the cells to produce higher amounts of it. This is useful when scientists want to study these proteins in the laboratory. You might want to study what they transport, their biochemical and biophysical properties, or to purify them to determine their 3D structures,' said the project in an interview with the IMI Programme Office. The DNA sequences are available at Addgene.org, which is a not-for-profit repository for this kind of reagents. Addgene sends the reagents on ReSOLUTE’s behalf for a small fee, which covers quality control and shipping costs. Any interested laboratory can order them directly from the Addgene website. In the few weeks that the material has been available, several labs worldwide have already requested the plasmids.
IMI’s RESOLUTE project has published the RESOLUTE Knowledge Base, an online database that brings together in one place information on a group of proteins called solute carriers (SLCs). ###SLCs are transport proteins that play an important role in controlling what molecules are allowed into and out of our cells. Although they have been implicated in diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and schizophrenia, SLCs have not yet been studied in detail. RESOLUTE aims to change that. Currently, the Knowledge Base, which is freely accessible to the scientific community, comprises high quality, reliable information from publicly available sources. ‘Public domain data on SLCs from multiple sources is compiled, connected and integrated, allowing SLC researchers to rapidly get an overview on the current knowledge on any human SLC transporter,’ explains Professor Giulio Superti-Furga, RESOLUTE academic coordinator from CeMM - the Research Center for Molecular Medicine of the Austrian Academy of Sciences. ‘This is a new milestone achieved by the RESOLUTE consortium and it is our first pillar to foster research on solute carriers. It will also allow RESOLUTE to become a reference hub for SLC research and open knowledge worldwide.’ In the coming years, RESOLUTE will add further information to the Knowledge Base from public resources as well as data generated by the project. RESOLUTE is due to end in 2023, but CeMM has committed to maintaining the Knowledge Base for a further 5 years after the end of the project.
ParticipantsShow participants on map
- Bayer Aktiengesellschaft, Leverkusen, Germany
- Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
- Novartis Pharma AG, Basel, Switzerland
- Pfizer Limited, Sandwich, Kent , United Kingdom
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
- Vifor (International) AG, St. Gallen, Switzerland
Universities, research organisations, public bodies, non-profit groups
- Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften Ev, Munich, Germany
- The University Of Liverpool, Liverpool, United Kingdom
- Universitat Wien, Vienna, Austria
- Universiteit Leiden, Leiden, Netherlands
- University of Oxford, Oxford, United Kingdom
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
- Axxam S.A, Bresso (Milan), Italy
- Cemm - Forschungszentrum Fuer Molekulare Medizin GMBH, Vienna, Austria
|Name||IHI funding in €|
|Axxam S.A||1 166 250|
|Cemm - Forschungszentrum Fuer Molekulare Medizin GMBH||6 692 438|
|Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften Ev||483 750|
|The University Of Liverpool||1 220 267|
|The University Of Manchester (left the project)||1 471|
|Universitat Wien||379 813|
|Universiteit Leiden||723 589|
|University of Oxford||1 332 424|
|Total Cost||12 000 002|