GameofGates SIGNED
Solute carrier proteins as the gates managing chemical access to cells
Total Cost €
0EC-Contrib. €
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Project "GameofGates" data sheet
The following table provides information about the project.
| Coordinator |
CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Organization address contact info |
| Coordinator Country | Austria [AT] |
| Project website | https://cemm.at/research/funding/international-funding/erc-advanced-grant-game-of-gates/ |
| Total cost | 2˙389˙782 € |
| EC max contribution | 2˙389˙782 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-AdG |
| Funding Scheme | ERC-ADG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-10-01 to 2021-09-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH | AT (WIEN) | coordinator | 2˙389˙782.00 |
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Project objective
Chemical exchange between cells and their environment occurs at cellular membranes, the interface where biology meets chemistry. Studying mechanisms of drug resistance, I realized that SoLute Carrier proteins (SLCs), not only represent the major class of small molecule transporters, but that they are encoded by one of the most neglected group of human genes. I identified a case where an SLC controls the activity of mTOR, suggesting that other SLCs may be involved in signalling. This formed the basis for the GameofGates project proposal. The name refers to SLCs as a metaphor for cellular gates coordinating access to resources following game rules that are largely unknown but worth learning, as the acquired knowledge could impact our understanding of cellular physiology and open avenues for innovative treatment of human diseases. GameofGates (GoG) plans the investigation of SLC function by comprehensively and deeply charting the genetic and protein interaction landscape of SLCs in a human cell line, while monitoring fitness, drug sensitivity and metabolic state. GoG aims at functionally de-orphanize many SLCs by assessing hundreds of thousands of genetic interactions as well as thousands protein and drug interactions. I hypothesize that SLC action is linked to signalling pathways and plays an important role in integration of metabolism and cell regulation for successful homeostasis. I propose that whole circuits of SLCs may be linked to particular nutrient auxotrophy states and that knowledge of these dependencies could instruct assessment of vulnerabilities in cancer cells. In turn, these could be pharmacologically exploited using existing or future drugs. Overall, GoG should position enough pieces into functional and regulatory networks in the SLC puzzle game to facilitate future work and motivate the community to embrace investigation of SLCs as conveyers of metabolic and chemical integration of cell biology with physiology and, in a wider scope, ecology.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Johannes W. Bigenzahn, Giovanna M. Collu, Felix Kartnig, Melanie Pieraks, Gregory I. Vladimer, Leonhard X. Heinz, Vitaly Sedlyarov, Fiorella Schischlik, Astrid Fauster, Manuele Rebsamen, Katja Parapatics, Vincent A. Blomen, André C. Müller, Georg E. Winter, Robert Kralovics, Thijn R. Brummelkamp, Marek Mlodzik, Giulio Superti-Furga LZTR1 is a regulator of RAS ubiquitination and signaling published pages: 1171-1177, ISSN: 0036-8075, DOI: 10.1126/science.aap8210 |
Science 362/6419 | 2020-01-29 |
| 2019 |
Anna Moskovskich, Ulrich Goldmann, Felix Kartnig, Sabrina Lindinger, Justyna Konecka, Giuseppe Fiume, Enrico Girardi, Giulio Superti-Furga The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-46952-9 |
Scientific Reports 9/1 | 2020-01-29 |
| 2018 |
Thomas Karonitsch, Richard K. Kandasamy, Felix Kartnig, Barbara Herdy, Karolina Dalwigk, Birgit Niederreiter, Johannes Holinka, Florian Sevelda, Reinhard Windhager, Martin Bilban, Thomas Weichhart, Marcus Säemann, Thomas Pap, Günter Steiner, Josef S. Smolen, Hans P. Kiener, Giulio Superti-Furga mTOR Senses Environmental Cues to Shape the Fibroblast-like Synoviocyte Response to Inflammation published pages: 2157-2167, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.04.044 |
Cell Reports 23/7 | 2020-01-29 |
| 2019 |
Astrid Fauster, Manuele Rebsamen, Katharina L. Willmann, Adrian César-Razquin, Enrico Girardi, Johannes W. Bigenzahn, Fiorella Schischlik, Stefania Scorzoni, Manuela Bruckner, Justyna Konecka, Katrin Hörmann, Leonhard X. Heinz, Kaan Boztug, Giulio Superti-Furga Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking published pages: 1138-1155, ISSN: 1350-9047, DOI: 10.1038/s41418-018-0192-6 |
Cell Death & Differentiation 26/6 | 2020-01-29 |
| 2018 |
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude, André C. Müller, Balázs Győrffy, Christopher R. Vakoc, Peter Valent, Keiryn L. Bennett, Johannes Zuber, Giulio Superti-Furga, Florian Grebien MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-04329-y |
Nature Communications 9/1 | 2020-01-29 |
| 2018 |
Mari Hashimoto, Enrico Girardi, Ruth Eichner, Giulio Superti-Furga Detection of Chemical Engagement of Solute Carrier Proteins by a Cellular Thermal Shift Assay published pages: 1480-1486, ISSN: 1554-8929, DOI: 10.1021/acschembio.8b00270 |
ACS Chemical Biology 13/6 | 2020-01-29 |
| 2018 |
Vitaly Sedlyarov, Ruth Eichner, Enrico Girardi, Patrick Essletzbichler, Ulrich Goldmann, Paula Nunes-Hasler, Ismet Srndic, Anna Moskovskich, Leonhard X. Heinz, Felix Kartnig, Johannes W. Bigenzahn, Manuele Rebsamen, Pavel Kovarik, Nicolas Demaurex, Giulio Superti-Furga The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification published pages: 766-774.e5, ISSN: 1931-3128, DOI: 10.1016/j.chom.2018.04.013 |
Cell Host & Microbe 23/6 | 2020-01-29 |
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