Objective
Anthracyclines belong to the most efficient drugs of cancer chemotherapy. However, their use is limited by severe cardiotoxicity, whose molecular triggers are not fully understood. Our aim is to analyse novel aspects of cardiac response to anthracyclines, namely signalling pathways regulating cardiac energetics. The ability to respond to altered energy supply or demand is particularly important for heart to maintain its contractile performance. Our approach will integrate a non-biased global analysis of antracycline-induced changes in gene expression and proteome/phospho-proteome with a targeted analysis of the signaling pathway of AMP-activated protein kinase (AMPK).
AMPK is a key sensor and regulator of cellular energy state and the drug reduces basic AMPK phosphorylation as we showed recently. The multidisciplinary approach combining biophysical, biochemical, molecular and physiological state-of-the-art techniques will (i) apply different model systems as recombinant protein, cultured cardiomyocytes, isolated perfused rat heart, and cancer cells for comparison, (ii) explore regulatory cross-talk between the AMPK cascade and other signalling pathways or key regulators of cardiac energy metabolism (e.g. creatine kinase), (iii) screen a library of cardioprotective compounds.
In scientific terms, we will identify anthracycline-induced changes in the cardiac energetic network and other signalling pathways susceptible to mediate drug cardiotoxic, and possibly anticancer effects. This can provide potent means to modulate drugs toxic and therapeutic activity. In terms of training, fellows goal is to acquire expertise in different cardiac models and in integrative approach (from molecular to physiological) to cardiac bioenergetics and non-scientific skills in a leading medically oriented research environment to amend her multidisciplinary portfolio with the long-term goal to obtain a permanent, leading position in research, e.g. as professor or clinical researcher.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics RNA transcriptomes
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
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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-MOBILITY-5
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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
GRENOBLE
France
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.