LEUKOCYTEFORCES

Cytoskeletal force generation and force transduction of migrating leukocytes

Coordinatore	Institute of Science and Technology Austria    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Austria [AT]
Totale costo	1˙458˙125 €
EC contributo	1˙458˙125 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-StG_20101109
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-04-01   -   2017-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	Institute of Science and Technology Austria  Organization address address: Am Campus 1 city: Klosterneuburg postcode: 3400 contact info Titolo: Dr. Nome: Michael Cognome: Sixt Email: send email Telefono: -15001 Fax: -13200	AT (Klosterneuburg)	hostInstitution	1˙458˙125.00
2	Institute of Science and Technology Austria  Organization address address: Am Campus 1 city: Klosterneuburg postcode: 3400 contact info Titolo: Ms. Nome: Carla Cognome: Mazuheli-Chibidziura Email: send email Telefono: +43 2243 9000 1038 Fax: +43 2243 9000 2000	AT (Klosterneuburg)	hostInstitution	1˙458˙125.00

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 Obiettivo del progetto (Objective)

'Cell migration is a universal feature of all metazoan life and crucially involved in most developmental, homeostatic and pathological processes. Most efforts to understand its molecular and mechanical aspects were focused on the “haptokinetic” paradigm. Here cells generate traction by coupling the protrusive and contractile forces of the actomyosin cytoskeleton via transmembrane receptors to the extracellular environment. Our recent work demonstrated that leukocytes, the class of animal cells that migrates with highest speed and efficiency, violate this paradigm. Once embedded in physiological three-dimensional matrices they instantaneously shift between adhesive and non-adhesive modes to transduce force. This proposal suggests a combined cell biological and biophysical approach to elucidate the molecular and mechanical principles underlying such plasticity. We will focus on the machinery most proximate to force generation and use genetics and pharmacology to characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments act in leukocytes migrating through environments of varying geometry and adhesive properties (Postdoc 1). Mechanical manipulations in conjunction with high resolution monitoring of substrate deformations will reveal how cytoskeletal force is transduced to the extracellular environment (Postdoc 2). In a technical support project (Technician) we will develop a cell-system with optimized access to stable genetic manipulations. Technically, these questions will be addressed by employing advanced live cell fluorescence imaging in combination with artificial environments engineered using microfluidics and substrate micropatterning. Importantly, findings will ultimately be challenged in living tissues. This multidisciplinary approach will generate an integrated view of locomotion-plasticity that will not only impact basic cell biology and immunology but also developmental and cancer biology.'