GENOMICDIFF

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

 Coordinatore 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

 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

Mappa


 Word cloud

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cells    gene    alterations    architecture    utilise    nuclear    transcription    perturbation    functional    distortion    stem    candidate    fate    expression    mesenchymal    mechanically    differentiation    host    cell    induced    chromatin    mechanobiology    genomic    mechanical   

 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.'

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