FUNCTIONALEDGE

Determining the roles of the nuclear periphery in mammalian genome function

 Coordinatore THE UNIVERSITY OF EDINBURGH 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙701˙090 €
 EC contributo 1˙701˙090 €
 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) 2010-03-01   -   2016-02-29

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    MEDICAL RESEARCH COUNCIL

 Organization address address: NORTH STAR AVENUE POLARIS HOUSE
city: SWINDON
postcode: SN2 1FL

contact info
Titolo: Dr.
Nome: Kate
Cognome: Wilson
Email: send email
Telefono: 441313000000
Fax: 441315000000

UK (SWINDON) beneficiary 142˙326.62
2    THE UNIVERSITY OF EDINBURGH

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024

UK (EDINBURGH) hostInstitution 1˙558˙763.40
3    THE UNIVERSITY OF EDINBURGH

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Prof.
Nome: Wendy
Cognome: Bickmore
Email: send email
Telefono: +44 131 3322471
Fax: +44 131 4678456

UK (EDINBURGH) hostInstitution 1˙558˙763.40

Mappa


 Word cloud

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loci    transcriptional    genome    organisation    determine    functional    edge    dna    periphery    inactive    spatial    differentiation    regions    centre    nuclear    maps    gene    chromatin    nucleus    positioning    human   

 Obiettivo del progetto (Objective)

'DNA sequence and epigenetic chromatin maps are important in understanding how genomes are regulated. However, these maps are linear and do not account for the three-dimensional context within which the genome functions in the cell. The spatial organisation of the genome in the nucleus is not random and is conserved in evolution, implying that it is under functional selection. This proposal aims to determine the functional significance of positioning specific genome regions at the edge of the nucleus in mammalian cells. The nuclear periphery has conventionally been considered as a zone of inactive chromatin and transcriptional repression. Several regulatory gene loci move away from the nuclear periphery as they are activated during differentiation. Novel approaches, developed by ourselves and others, that allow genomic regions to be relocated from the centre of the nucleus to the periphery, have directly shown that proximity to the nuclear edge can down-regulate human gene expression. We propose to dissect the pathways that mediate this spatially-defined transcriptional regulation, to determine what features make certain genes susceptible to it, to establish the functional consequences of preventing gene repositioning during differentiation, and to examine defects of the periphery found in premature ageing. A neglected hypothesis is that positioning of inactive chromatin against the nuclear periphery is a mechanism to minimize DNA damage on sequences in the nuclear centre. We will determine whether mutation rate is altered when loci are repositioned towards the nuclear periphery. By experimentally remodelling the spatial organisation of the genome, this proposal goes beyond the current descriptive phase of 3D nuclear organisation, into an understanding of its functional consequences on multiple aspects of genome function. It will also aid in understanding human diseases characterised by alterations of the nuclear periphery.'

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KRABNKAP (2011)

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