Characterization of a neurogenic programme activated by the proneural factor Mash1. (360G-Wellcome-082347_B_07_Z)

£134,651

Our first aim in this application is to characterize the neurogenic programme activated by the proneural bHLH protein Mash1 in neural stem cells. We will use an inducible Mash1-expressing neural stem cell line to identify on a genome wide basis the sequences bound by Mash1 and the genes associated with these sequences. To achieve this aim, we will use the ChIP-PET technique in collaboration with the Genome Institute of Singapore, complemented by expression arrays, bioinformatic analysis and hybridization of chromatin immunoprecipitation products to genomic microarrays (ChIP on chip). Our second aim is to characterize the mechanisms that underpin the regulation of Mash1 target genes in differentiating neural stem cells. Hybridization of expression arrays at different time points will define the time course of expression of Mash1 targets. ChIP on chip experiments with antibodies to Mash1, to various histone modifications and to candidate Mash1 co-factors will determine the contribution of Mash1 binding site occupancy, cofactor recruitment and histone acetylation and metylation to the regulation of Mash1 targets, and particularly to their timing of expression. We will validate the results obtained in cultured neural stem cells by performing chromatin immunoprecipitation experiments with embryonic brain material.

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Grant Details

Amount Awarded 134651
Applicant Surname Buckley
Approval Committee Molecular and Cellular Neuroscience Funding Committee
Award Date 2007-05-03T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 082347/B/07/Z
Lead Applicant Prof Noel Buckley
Other Applicant(s) Prof Francois Guillemot
Partnership Value 134651
Planned Dates: End Date 2012-06-30T00:00:00+00:00
Planned Dates: Start Date 2007-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London