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Add medical genetic solutions to RESOLUTE (REsolution)

Objective

Solute carriers (SLCs) are the largest family of membrane transporters encoded in the human genome and their role in trafficking nutrients, ions, vitamins and cofactors is vital for maintaining homeostasis in individual cells, organs and tissues. Their misfunction is associated with a variety of diseases and a small number of individual SLCs are successful drug targets. Despite their importance, SLCs remain understudied and a surprisingly large proportion is deemed “orphan” in terms of transport function. The ongoing RESOLUTE IMI consortium is working on the systematic de-orphanization of SLCs and is highly successful in creating open-access tools, high-throughput assays and omics data. This effort is focused on basic aspects of SLC biochemistry and biology and was not meant to include the medical dimension. In the REsolution program we propose here, we exploit the unique opportunity to now link the RESOLUTE knowledge to physiology and disease through human genetics. 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. Concretely, we plan to: 1) assemble human SLC genetic information and annotate within the RESOLUTE knowledgebase; 2) study the structure-activity relationship for selected SLC variants, 3) use deep mutagenesis and artificial intelligence to develop the equivalent of a “Rosetta stone” allowing the interpretation of SLC genetic variation. This will allow us to not only contextualize SLCs, as elucidated by RESOLUTE, 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.

Call for proposal

H2020-JTI-IMI2-2020-22-single-stage
See other projects for this call

Coordinator

CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Address
Lazarettgasse 14 Akh Bt 25.3
1090 Wien
Austria
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 642 222,50

Participants (8)

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 20 000
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 20 000
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
AXXAM SPA
Italy
EU contribution
€ 175 000
Address
Via Meucci 3
20091 Bresso Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
UNIVERSITEIT LEIDEN
Netherlands
EU contribution
€ 20 000
Address
Rapenburg 70
2311 EZ Leiden
Activity type
Higher or Secondary Education Establishments
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 20 000
Address
Hofgartenstrasse 8
80539 Munchen
Activity type
Research Organisations
UNIVERSITAT WIEN
Austria
EU contribution
€ 102 777,50
Address
Universitatsring 1
1010 Wien
Activity type
Higher or Secondary Education Establishments
PFIZER LIMITED
United Kingdom
EU contribution
€ 0
Address
Ramsgate Road
CT13 9NJ Sandwich
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
BAYER AKTIENGESELLSCHAFT
Germany
EU contribution
€ 0
Address
Kaiser-wilhelm-allee 1
51373 Leverkusen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)