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GRADIENTSENSING SIGNED

Cellular navigation along spatial gradients

Total Cost €

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EC-Contrib. €

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Partnership

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 GRADIENTSENSING project word cloud

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

suitable    guidance    first    intravital    immunity    dictyostelium    tools    temporal    cells    depends    sensing    migration    gradients    cell    validated    cellular    molecules    holistic    proteins    newly    genome    concentration    engineering    eukaryotic    genetic    chemotaxis    differences    contribution    image    editing    immune    position    tractable    assaying    quantitative    signalling    vivo    genetically    directionally    primary    shape    orchestration    direction    immobilized    malignancy    central    amoeba    triggered    engineered    gradient    fundamental    shapes    critically    employing    microscopy    function    haptotaxis    extracellular    engineer    chemokine    cancer    permanently    cues    persistent    family    cyclicamp    migrating    spatial    emerge    leukocyte    precision    immunology    suggest    perform    responding    motile    combination    mechanistic    inferred    soluble    guarantee    convergent    biological    leukocytes    screen    principles    interpreted    physiological    question    complementary    biology    discoideum    specify    relevance    chemokines    optogenetically    diverse    spatiotemporal    paradigms    signals   

Project "GRADIENTSENSING" data sheet

The following table provides information about the project.

Coordinator
INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA 

Organization address
address: Am Campus 1
city: KLOSTERNEUBURG
postcode: 3400
website: www.ist.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]
 Total cost 1˙984˙922 €
 EC max contribution 1˙984˙922 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA AT (KLOSTERNEUBURG) coordinator 1˙984˙922.00

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 Project objective

Gradients of extracellular signalling molecules are a central concept in biology: for example gradients of guidance-cues such as chemokines position migrating cells in development, malignancy and immunity. Because immune cells are permanently motile, their function most critically depends on spatiotemporal orchestration by a large family of chemokines. To specify direction, concentration differences of the chemokine need to be interpreted by the migrating cell. Most mechanistic knowledge about eukaryotic gradient sensing is inferred from the amoeba Dictyostelium discoideum migrating towards soluble gradients of cyclicAMP. The biology of chemokines is much more diverse, e.g. gradients can take different shapes and, importantly, they do not only emerge in the soluble but also in the immobilized phase. In this proposal we suggest to address the principles of leukocyte chemotaxis using convergent system wide, cell biological and intravital approaches. Employing a newly developed, genetically tractable primary leukocyte system, we will test the contribution of spatial and temporal signalling paradigms of gradient sensing. Quantitative microscopy will be used to image cellular responses to engineered immobilized and soluble chemokine gradients of defined shape as well as to optogenetically triggered signals. In a complementary approach we will screen for proteins responding to chemokine signalling and perform the first genome wide genome editing-based loss of function screen for directionally persistent chemotaxis and haptotaxis. Findings will be validated in vivo to guarantee physiological relevance. In a support project we will precision-engineer the genome of primary leukocytes suitable for assaying migration. A unique combination of cellular, genetic, engineering and quantitative microscopy tools will allow this new and holistic approach to a question which is not only fundamental for immunology but also for understanding development and cancer biology.

 Publications

year authors and title journal last update
List of publications.
2019 Jörg Renkawitz, Aglaja Kopf, Julian Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, Erik S. Welf, Gaudenz Danuser, Reto Fiolka, Michael Sixt
Nuclear positioning facilitates amoeboid migration along the path of least resistance
published pages: 546-550, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1087-5
Nature 568/7753 2020-03-23
2018 Miroslav Hons, Aglaja Kopf, Robert Hauschild, Alexander Leithner, Florian Gaertner, Jun Abe, Jörg Renkawitz, Jens V. Stein, Michael Sixt
Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells
published pages: 606-616, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0109-z
Nature Immunology 19/6 2020-03-23
2018 Alexander Leithner, Joerg Renkawitz, Ingrid De Vries, Robert Hauschild, Hans Häcker, Michael Sixt
Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration
published pages: 1074-1077, ISSN: 0014-2980, DOI: 10.1002/eji.201747358
European Journal of Immunology 48/6 2020-03-23

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