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GameofGates SIGNED

Solute carrier proteins as the gates managing chemical access to cells

Total Cost €

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EC-Contrib. €

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Partnership

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 GameofGates project word cloud

Explore the words cloud of the GameofGates project. It provides you a very rough idea of what is the project "GameofGates" about.

occurs    homeostasis    auxotrophy    charting    thousands    slcs    nutrient    human    puzzle    class    ecology    integration    interface    mechanisms    conveyers    refers    carrier    learning    fitness    controls    regulatory    innovative    line    name    environment    functionally    de    largely    landscape    metaphor    signalling    avenues    cells    dependencies    position    formed    chemical    acquired    monitoring    cell    resistance    networks    exploited    cellular    mtor    comprehensively    suggesting    plans    circuits    embrace    scope    investigation    gates    physiology    interaction    hypothesize    sensitivity    exchange    protein    slc    unknown    gog    gameofgates    hundreds    diseases    action    transporters    realized    orphanize    motivate    group    treatment    worth    basis    interactions    instruct    metabolism    deeply    assessing    successful    biology    solute    game    drugs    linked    plays    function    chemistry    metabolic    drug    pharmacologically    vulnerabilities    genes    functional    rules    turn    meets    molecule    cancer    community    genetic    small    membranes    proteins    regulation    pieces    encoded   

Project "GameofGates" data sheet

The following table provides information about the project.

Coordinator
CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH 

Organization address
address: LAZARETTGASSE 14 AKH BT 25.3
city: WIEN
postcode: 1090
website: http://www.oeaw.ac.at/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
1    CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH AT (WIEN) coordinator 2˙389˙782.00

Map

 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
List of publications.
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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