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GRADIENTSENSING SIGNED

Cellular navigation along spatial gradients

Total Cost €

0

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.

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

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

Map

 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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