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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2008-AdG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
EH8 9YL Edinburgh
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.