MEMORY CONTROL

Memory control; Molecular mechanisms underlying the scope of immunological memory

Coordinatore	Academisch Medisch Centrum bij de Universiteit van Amsterdam    more  Organization address address: MEIBERGDREEF 9 city: AMSTERDAM postcode: 1105AZ contact info Titolo: Mr. Nome: Edwin Cognome: Groenewegen Van Wijk Email: send email Telefono: 31205660075 Fax: 31205669698
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	75˙000 €
EC contributo	75˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2017-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	Academisch Medisch Centrum bij de Universiteit van Amsterdam  Organization address address: MEIBERGDREEF 9 city: AMSTERDAM postcode: 1105AZ contact info Titolo: Mr. Nome: Edwin Cognome: Groenewegen Van Wijk Email: send email Telefono: 31205660075 Fax: 31205669698	NL (AMSTERDAM)	coordinator	75˙000.00

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 Obiettivo del progetto (Objective)

'T cell mediated immunity protects us against pathogens and cancer. The naïve T cell pool consists of millions of clones, each one unique based on its T cell receptor (TCR). Upon infection, only a few of these clones are recruited to generate antigen-specific memory. Selection of memory clones is a trade-off between specificity and diversity; too much specificity restricts antigen-recognition, which precludes responsiveness against pathogens with small mutations. Too much diversity impairs efficiency of recall responses. Mechanisms controlling memory diversity are largely unknown. In this project I will identify and characterize the role of molecules that control memory cell diversity to answer the question whether optimal diversity is inherently present in the immune system or may be adjusted to benefit vaccine strategies. I will set up novel in vitro models for the generation of memory cells and analysis of the role of TCR-affinity on memory cell formation using murine cells. With this platform, I will perform high-throughput screening for the identification of potential target genes involved in the regulation of TCR affinity-dependent memory cell formation. In addition, a new mouse model will be generated for the specific deletion of genes in memory T cells. This system will be used to verify the in vivo effects of candidate genes on memory cell diversity. Finally, I will demonstrate the clinical relevance of our murine findings by corroborating our observations with novel human cell culture systems. In summary, I propose to investigate a currently underappreciated aspect of immunity. Our technological and scientific innovations ensure rapid generation of new, relevant and high-impact data. Elucidation of the mechanisms that mediate memory cell diversity are of high relevance, as it allows a more rational design of vaccines that require broad neutralizing (e.g. against influenza or HIV), or highly specific (e.g. against cancer) responses.'