Objective
This project addresses robustness of phenotypic function on the basis of highly interlinked network topologies on a very practical level: Synthetic Lethality - as proposed for novel cancer treatment regimes. Function in this context is the property of transformed cells to continuously divide, and robustness is encoded by regulatory elements on the genomic and proteomic level triggering drug treatment escape as an emergent property: chemotherapy resistance.
This project will derive novel concepts, methodologies, and their algorithmic implementation for annotation and analysis of general regulatory networks - with particular focus on network robustness and escape routes toward maintaining function. In parallel, computational genomics will be applied on a gene expression data set derived from a unique, systematic collection of chemotherapy resistant cancer cell lines. These real world data encode a set of regulatory escape mechanisms to overcome the lethality imposed by specific drug.
The general concepts and approaches - focusing on dynamical levels - will subsequently be calibrated and merged with results from computational genomics - focusing on a static system representation - to gain insight into the mechanisms of cancer cell robustness, but in particular to identify key proteins of cellular escape mechanisms to overcome lethality of drugs. Blocking these proteins may result in synthetic lethality including re-sensitization of chemoresistant cancer cells to cytotoxic drugs.
To prove the validity of our Complex Systems Analysis approach we will test generated hypotheses on synthetically lethal hubs in the cellular control network via experimental knock down experiments utilizing siRNA. This project will provide further insight into dynamical hierarchies of structure and control on a general level, will calibrate methodologies for their use in computational biology, and will test the validity of these approaches for identifying novel routes in cancer treatment.
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.
- natural sciences biological sciences genetics
- natural sciences mathematics pure mathematics topology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- engineering and technology electrical engineering, electronic engineering, information engineering information engineering telecommunications telecommunications networks
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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.
FP6-2005-NEST-PATH
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.
Coordinator
MÜNCHEN
Germany
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.