GENOMICDIFF

The biophysical regulation of genome function and its role in mesenchymal stem cell differentiation

Coordinatore	QUEEN MARY UNIVERSITY OF LONDON    more  Organization address address: 327 MILE END ROAD city: LONDON postcode: E1 4NS contact info Titolo: Prof. Nome: David A. Cognome: Lee Email: send email Telefono: +44 20 7882 8874
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	200˙371 €
EC contributo	200˙371 €
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-2011-IEF
Funding Scheme	MC-IEF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-05-01   -   2014-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	QUEEN MARY UNIVERSITY OF LONDON  Organization address address: 327 MILE END ROAD city: LONDON postcode: E1 4NS contact info Titolo: Prof. Nome: David A. Cognome: Lee Email: send email Telefono: +44 20 7882 8874	UK (LONDON)	coordinator	200˙371.80

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 Obiettivo del progetto (Objective)

'Little is known concerning the mechanisms through which mechanical stimuli are transduced into regulatory signals within the cell. Gene expression can be regulated through alterations in nuclear architecture, modulating genome function. Mechanical load induces both nuclear distortion and alterations in gene expression. One putative transduction mechanism involves changes in gene expression in response to alterations in nuclear architecture as a result of mechanical perturbation of the cell. Additionally, remodelling of the nucleus occurs during stem cell differentiation, altering nuclear stiffness, and potentially influences nuclear architecture mediated mechanoregulation of gene transcription.

In this project, the candidate will utilise the expertise in mechanobiology and functional genomics available at the host institution to investigate the potential for the micro-mechanical environment to modulate MSC differentiation fate via changes in nuclear architecture. Accordingly, the candidate proposes an ambitious and innovative program of research to test the following hypotheses: 1. Mechanically-induced nuclear distortion causes alterations to the nuclear architecture and chromatin dynamics sufficient to alter gene transcription 2. Mechanically-induced differentiation can lead to inheritable changes in the epigenetic state of chromatin regulating mesenchymal stem cell fate commitment

He will employ a multidisciplinary approach building on the strengths of the host institution. The studies will utilise human mesenchymal stem cells in conjunction with state-of-the-art techniques for the mechanical perturbation of cells, functional analysis of nuclear organisation, biomechanical analysis, and functional genomic analysis; which will act to maintain and enhance the candidate’s position at the forefront of advances in this newly emerging field of genomic mechanobiology.'