COCO

The molecular complexity of the complement system

Coordinatore	UNIVERSITEIT UTRECHT    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	1˙700˙000 €
EC contributo	1˙700˙000 €
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-2008-AdG
Funding Scheme	ERC-AG
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-04-01   -   2014-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITEIT UTRECHT  Organization address address: Heidelberglaan 8 city: UTRECHT postcode: 3584 CS contact info Titolo: Ms. Nome: Liesbeth Cognome: Bos-Klomp Email: send email Telefono: +31 30 2533939 Fax: +31 30 2531645	NL (UTRECHT)	hostInstitution	1˙700˙000.00
2	UNIVERSITEIT UTRECHT  Organization address address: Heidelberglaan 8 city: UTRECHT postcode: 3584 CS contact info Titolo: Prof. Nome: Piet Cognome: Gros Email: send email Telefono: -2533126 Fax: -2533939	NL (UTRECHT)	hostInstitution	1˙700˙000.00

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 Obiettivo del progetto (Objective)

'The complement system is a regulatory pathway in mammalian plasma that enables the host to recognize and clear invading pathogens and altered host cells, while protecting healthy host tissue. This regulatory system consists of ~30 large multi-domain plasma and cell-surface proteins, that act in concert through an interplay of proteolysis and complex formations on target membranes. We study the molecular events on membranes that ensure initiation and amplification of the response, protection of host cells and activation of immune responses leading to cell lysis, phagocytosis and B-cell stimulation.

In the past few years, we have resolved the structural details of the large complement proteins involved in the central, aspecific labelling and amplification step; with recent data we revealed the structural basis of the assembly and activity of the protease complex associated with this step. These insights into the central aspecific reaction, and the experiences gained on working with these large multi-domain proteins and complexes, give us an excellent starting point to addres the questions of specificity, protection and activation of immune cells.

The goal of the proposal is to elucidate the multivalent molecular mechanisms of recognition, regulation and immune cell activation of the complement system on target membranes. We will use protein crystallography and electron microscopy to study the interactions and conformational changes involved in protein complex formation, and (single-molecule) fluorescence to resolve the multivalent molecular events, the conformational states and transitions that occur on the membrane. The combined data will provide mechanistic insights into the specifity of immune clearance by the complement system.

Understanding the molecular mechanisms of complement activation and regulation will be instrumental in developing more potent therapeutics to control infections, prevent tissue damage and fight tumours by immunotherapies.'