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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.

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

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

Map

 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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