ZINC-HUBS

Engineering zinc fingers to target cancer hub genes

Coordinatore	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	1˙327˙689 €
EC contributo	1˙327˙689 €
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-2007-StG
Funding Scheme	ERC-SG
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-10-01   -   2014-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACIO CENTRE DE REGULACIO GENOMICA  Organization address address: CARRER DOCTOR AIGUADER 88 city: BARCELONA postcode: 8003 contact info Titolo: Mr. Nome: Stefan Cognome: Pönisch Email: send email Telefono: +34 93 3160264 Fax: +34 93 3969983	ES (BARCELONA)	beneficiary	0.00
2	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE  Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD city: LONDON postcode: SW7 2AZ contact info Titolo: Dr. Nome: Mark Cognome: Isalan Email: send email Telefono: +44 207 59 46482 Fax: +44 207 59 46482	UK (LONDON)	hostInstitution	0.00
3	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE  Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD city: LONDON postcode: SW7 2AZ contact info Titolo: Ms. Nome: Brooke Cognome: Alasya Email: send email Telefono: +44 207 594 1181 Fax: +44 207 594 1418	UK (LONDON)	hostInstitution	0.00

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 Obiettivo del progetto (Objective)

'For the last ten years, protein engineering technologies have been developed to make zinc finger peptides to recognise a wide variety of user-defined DNA sequences. This has enabled the construction of synthetic transcription factors that can upregulate or repress target genes at will. More recently, synthetic zinc fingers have been linked to nucleases to direct double stranded breaks at desired loci within genomes. These breaks increase the efficiency of homologous recombination so that, by providing an exogenous repair sequence, it is possible to repair or mutate endogenous genes. Although zinc finger engineering has reached a state of maturity, there are very few groups in the world who have the technical know-how to adopt this technology, and this has delayed general uptake. We will use the expertise we have developed, in both zinc finger engineering and gene repair, to construct zinc finger proteins to recognise some of the most highly-connected (and widely-studied) genes in biology. This will serve as a toolkit for the research community to target hub genes and either mutate or repair them. As a starting point we propose to target the following hub genes: TBP (TATA-binding protein), p53, p300, RXR, pRB, RelA, c-jun, c-myc, and c-fos. These genes are the most connected hubs in the human transcription factor network (TRANSFAC 8.2 database) and their mutants are associated with a variety of diseases. We will engineer and characterise zinc finger proteins that recognise these DNA sequences in vitro and induce gene repair in vivo. For example, this will allow cancer cell lines to have particular oncogenes repaired or mutated, within the context of all the other mutations that have been accrued during the process of oncogenesis. This will help to characterise the contribution of network nodes and hubs to the observed phenotypes. Ultimately, some of the gene repair peptides we create will have therapeutic potential, as well as providing tools for systems biology.'