Systematic Chemical Genetic Interrogation of Biological Networks


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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 2˙400˙000 €
 EC contributo 2˙400˙000 €
 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-2008-AdG
 Funding Scheme ERC-AG
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-08-01   -   2014-07-31


# participant  country  role  EC contrib. [€] 

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

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024
Fax: +44 131 650 9023

UK (EDINBURGH) hostInstitution 2˙400˙000.00

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

contact info
Titolo: Prof.
Nome: Michael David
Cognome: Tyers
Email: send email
Telefono: -7764
Fax: -6116

UK (EDINBURGH) hostInstitution 2˙400˙000.00


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

chemical    networks    cell    therapeutic    genetic    predict    magic    biological    interactions    discovery    small    function    network    cgm    combinations    species    functional    yeast    gene    genome    manipulate    drug    molecule    selectively   

 Obiettivo del progetto (Objective)

'Recent genome-scale studies have revealed the massive redundancies and functional interconnectivities encoded by the genome. For example, the budding yeast Saccharomyces cerevisiae is predicted to harbor 200,000 synthetic lethal interactions. This genetic density has profound implications for both understanding the architecture of living systems and drug discovery. In particular, the dense connections of biological networks mandate a multi-node strategy to selectively manipulate any given biological response, whether it be to probe system level properties or for therapeutic intervention in human disease. By analogy to Ehrlich s magic bullet concept, we term this approach the magic shotgun . We propose to systematically identify chemical-genetic interactions that selectively disrupt any specific mutant genotype and chemical-chemical interactions that selectively kill pathogenic species. Our five main objectives are: (i) construct a comprehensive Chemical Genetic Matrix (CGM) of small molecule-gene interactions in order to predict chemical synergies and manipulate network function in a species-specific manner; (ii) elaborate the CGM with a set of ~5,000 yeast bioactive molecules derived from high throughput/high content screens; (iii) identify small molecule combinations that modulate stem cell and cancer cell renewal and differentiation; (iv) define compound mechanisms of action by functional genomics; (v) integrate chemical-genetic, genetic and protein interaction datasets to predict gene function, small molecule targets and network properties. This research will cross-connect genetic pathways through chemical space, identify species-specific combinations of agents as therapeutic leads and provide a repository of small molecule probes for cell biological and systems-level analysis. The principles developed through the course of this work will raise our understanding of biological networks and help establish a new approach to drug discovery.'

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