MHC CLASS II-OMICS

Towards understanding and manipulation of MHC class II antigen presentation

 Coordinatore STICHTING HET NEDERLANDS KANKER INSTITUUT 

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 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 2˙112˙300 €
 EC contributo 2˙112˙300 €
 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-2009-AdG
 Funding Scheme ERC-AG
 Anno di inizio 2010
 Periodo (anno-mese-giorno) 2010-09-01   -   2015-08-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Henri
Cognome: Van Luenen
Email: send email
Telefono: 31205122097
Fax: 31206691383

NL (AMSTERDAM) hostInstitution 2˙112˙300.00
2    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Prof.
Nome: Jacobus Jozef Cornelis
Cognome: Neefjes
Email: send email
Telefono: 31205122017
Fax: 31205122029

NL (AMSTERDAM) hostInstitution 2˙112˙300.00

Mappa


 Word cloud

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performed    manipulating    auto    molecules    cell    clustered    experiments    hits    screen    mhc    affecting    sub    expression    facs    biological    class    compounds    chemical    immune    biology    sirna    combinations    peptide    responses    networks    disease    antigen    presentation   

 Obiettivo del progetto (Objective)

'MHC class II molecules are crucial for specific immune responses. In a complicated series of cell biological events, they catch a peptide in the endosomal route for presentation at the plasma membrane to the immune system. At present some 20 factors have been identified as involved in the process of MHC class II antigen presentation that are potential targets for manipulating these responses as MHC class II molecules are involved in most auto-immune diseases. Defining further targets for manipulating MHC class II responses would have implications for various disease states when these can be inhibited by chemical compounds or biologicals. We have performed a genome-wide FACS-based siRNA screen for molecules affecting MHC class II expression and peptide loading. After 100.000 individual 2-color FACS analyses, we identified 276 proteins that can be functionally sub-clustered for expression and for cell biological effects. We now propose to study the cell biology of these 276 hits to elucidate the molecular and cell biological mechanisms of MHC class II antigen presentation (the MHC class II-ome). As a first step, the 276 hits are sub-clustered for effects on MHC class II transcription or cell biology. These sub-clusters may correspond to networks. We propose to validate and extend these networks by experiments by a team of scientists concentrating on the various aspects of the cell biology of MHC class II antigen presentation. A parallel chemical compound screen will be performed to identify compounds affecting MHC class II antigen presentation. By cross-correlating the biological phenotypes of compounds with those of siRNA silencing, novel target-lead combinations will be defined by reciprocal chemical genetics. Our experiments should result in a global understanding of MHC class II antigen presentation. In addition, it should reveal target-lead combinations for manipulation of MHC class II antigen presentation in infection, auto-immune disease and transplantation.'

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