THPLAST

The molecular regulation of T helper cell subtype plasticity

Coordinatore	GENOME RESEARCH LIMITED    more  Organization address address: THE GIBBS BUILDING, EUSTON ROAD 215 city: LONDON postcode: NW1 2BE contact info Titolo: Mr. Nome: David Cognome: Davison Email: send email Telefono: +44 1223 834244
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	211˙092 €
EC contributo	211˙092 €
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-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-08-08   -   2014-02-04

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	GENOME RESEARCH LIMITED  Organization address address: THE GIBBS BUILDING, EUSTON ROAD 215 city: LONDON postcode: NW1 2BE contact info Titolo: Mr. Nome: David Cognome: Davison Email: send email Telefono: +44 1223 834244	UK (LONDON)	coordinator	211˙092.80
2	MEDICAL RESEARCH COUNCIL  Organization address address: NORTH STAR AVENUE POLARIS HOUSE city: SWINDON postcode: SN2 1FL contact info Titolo: Ms. Nome: Elizabeth Cognome: Cutler Email: send email Telefono: +44 122 340 2357	UK (SWINDON)	participant	0.00

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 Obiettivo del progetto (Objective)

'Naïve CD4 T cell differentiate into distinct lineages to achieve successful adaptive immune responses to diverse categories of pathogens. The development of these effector cells is controlled by cytokines, transcription factor interactions and chromatin modifications. In addition, several of the differentiated subtypes can interconvert, a property known as plasticity. However, the molecular regulation of flexibility of this subset cells is still unresolved. I propose to explore the molecular machinery of the T helper (Th) effector cells’ plasticity, specifically of Th subset 2 plasticity to Th1, as understanding of this reprogramming is a key target of autoimmune- and allergen-specific immunotherapy. I plan to study the regulation of Th2-Th1 cell plasticity both experimentally and computationally. I will identify the gene expression level dynamics as well as the epigenetic events during plasticity using RNA- and ChIP-deep sequencing. These results will be processed by computational tools to define the hierarchy and dynamics of molecular regulators, and to predict key molecular players (transcription factors, microRNAs) responsible for expression of the specific cytokines. I will also monitor specific RNA and protein expression at a single cell level, and identify specific regulatory interactions, including the nucleic acid motifs involved. This research will reveal insights into the balance between lineage commitment and plasticity, which is a key question in developmental biology, and in general will impact a wide range of areas in biology from stem cell biology to cancer.'