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SAMNets SIGNED

Investigation of adaptive design and rewiring of Survival-Apoptosis-Mitogenic (SAM) signalling transduction network

Total Cost €

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EC-Contrib. €

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Partnership

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 SAMNets project word cloud

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

skills    gene    predict    fate    biology    expression    stns    combinations    acquire    rassf1    qualify    techniques    stn    depending    background    life    model    networks    signal    connecting    site    property    mek    network    molecule    protein    lines    egfr    correlated    mutational    small    mitogenic    environment    interconnecting    mechanistic    reconstruction    intrinsic    relate    perturbations    decisions    pi3k    multiple    intuitive    context    predictions    topology    computational    single    erk    mst    intracellular    survival    apoptotic    question    inhibitors    answer    transduction    integrate    modern    molecules    ras    genetic    dependence    integration    mutations    dynamic    raf    actions    acquired    akt    environmental    levels    validated    experimentally    reconstructed    emerges    treatment    reasoning    compute    molecular    models    landscapes    outputs    signalling    pten    drug    concerted    signals    picked    mechanisms    parts    lats    data    sam    efficient    uniquely    panel    dry    career    scope    resistances    understand    training    biochemical    significantly    he    cellular    cell    prospects    wet   

Project "SAMNets" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN 

Organization address
address: BELFIELD
city: DUBLIN
postcode: 4
website: www.ucd.ie

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 Ireland [IE]
 Project website http://www.ucd.ie/sbi/people/groups/kholodenkogroup/
 Total cost 187˙866 €
 EC max contribution 187˙866 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-05-01   to  2019-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN IE (DUBLIN) coordinator 187˙866.00

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 Project objective

Cell life is not the property of any single protein or gene; rather it emerges from concerted actions of multiple molecules in cellular networks. Current proposal is focused on Signal Transduction Networks (STN) connecting the environment to cell responses. A major challenge is to understand how STN integrate and process environmental signals in a robust and reliable way and how they “compute” cell fate decisions depending on genetic background. To answer this question, the study will be focused on three interconnecting STNs: the Survival (PI3K/PTEN/AKT), Apoptotic (RASSF1/MST/LATS) and Mitogenic (EGFR/RAS/RAF/MEK/ERK) pathways, the SAM network. In the scope of current proposal the methods of signalling network reconstruction will be improved and the SAM network topology will be reconstructed in the panel of cell lines. Based on available data and reconstructed network topology the mechanistic site-specific dynamic model of SAM network will be developed and validated. Model predictions of dependence of signalling outputs behaviour on different perturbations (like small molecule inhibitors and their combinations) and background (mutations and protein expression levels) will be validated. The signalling outputs will be experimentally correlated to the cell fate decisions.

The developed models will relate mutational information to treatment responses in the context of different expression landscapes and they will explain and predict mechanisms of intrinsic and acquired drug resistances, which often cannot be picked up by only intuitive reasoning. During the project the applicant will get training in a range of modern computational modelling, biochemical and molecular biology techniques used to study intracellular signalling networks. As a result, he will acquire skills of efficient integration of wet and dry parts of systems biology which will uniquely qualify him in the field significantly enhancing his career prospects.

 Publications

year authors and title journal last update
List of publications.
2019 Keesha E. Erickson, Oleksii S. Rukhlenko, Richard G. Posner, William S. Hlavacek, Boris N. Kholodenko
New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling
published pages: 162-173, ISSN: 1044-579X, DOI: 10.1016/j.semcancer.2018.02.008
Seminars in Cancer Biology 54 2019-09-04
2018 Oleksii S. Rukhlenko, Fahimeh Khorsand, Aleksandar Krstic, Jan Rozanc, Leonidas G. Alexopoulos, Nora Rauch, Keesha E. Erickson, William S. Hlavacek, Richard G. Posner, Silvia Gómez-Coca, Edina Rosta, Cheree Fitzgibbon, David Matallanas, Jens Rauch, Walter Kolch, Boris N. Kholodenko
Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling
published pages: 161-179.e14, ISSN: 2405-4712, DOI: 10.1016/j.cels.2018.06.002
Cell Systems 7/2 2019-09-04
2019 Daniel Lill, Oleksii S. Rukhlenko, Anthony James Mc Elwee, Eugene Kashdan, Jens Timmer, Boris N. Kholodenko
Mapping connections in signaling networks with ambiguous modularity
published pages: , ISSN: 2056-7189, DOI: 10.1038/s41540-019-0096-1
npj Systems Biology and Applications 5/1 2019-09-04
2019 Keesha E. Erickson, Oleksii S. Rukhlenko, Md Shahinuzzaman, Kalina P. Slavkova, Yen Ting Lin, Ryan Suderman, Edward C. Stites, Marian Anghel, Richard G. Posner, Dipak Barua, Boris N. Kholodenko, William S. Hlavacek
Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor
published pages: e1006706, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006706
PLOS Computational Biology 15/1 2019-09-04
2018 Tapesh Santra, Oleksii Rukhlenko, Vadim Zhernovkov, Boris N. Kholodenko
Reconstructing static and dynamic models of signaling pathways using Modular Response Analysis
published pages: 11-21, ISSN: 2452-3100, DOI: 10.1016/j.coisb.2018.02.003
Current Opinion in Systems Biology 9 2019-09-04
2018 Caterina Thomaseth, Dirk Fey, Tapesh Santra, Oleksii S. Rukhlenko, Nicole E. Radde, Boris N. Kholodenko
Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstruction
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-34353-3
Scientific Reports 8/1 2019-09-04

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