Objective
Familial hypertrophic cardiomyopathy (FHC) is a myocardial disease with the major feature of asymmetric septal hypertrophy (ASH). It is one of the most common monogenic diseases with a disease prevalence of 1:500 in young adults. It is the major cause of s udden death in the young and is associated with a significant risk of heart failure. The major objective of the present project is the elucidation of the mechanisms by which cardiac myosin-binding protein C (cMyBP-C) mutations lead to FHC. Particularly, we will investigate two new concepts, the first one emerging from our recent data: (1) Impairment by truncated cMyBP-C mutants of the ubiquitin-proteasome system (UPS) as a pathogenic factor of FHC and (2) Specific mobilization and differentiation of recent ly identified Isl-1 positive cardioblasts as a cause of ASH. Other objectives concern the role of cMyBP-C in sarcomere structure and its phosphorylation in regulation of cardiac contraction. The recent development of two targeted cMyBP-C mice by L. Carrier will allow to resolve these issues. The heterozygous cMyBP-C null mice is the first model with ASH and will therefore enable us to identify the cause of this enigmatic alteration. L. Carrier and the Eschenhagen lab recently demonstrated that truncated cMy BP-Cs are substrates and inhibitors of the UPS. Impairment of the UPS in the pathogenesis of FHC is a novel concept in cardiology, which parallels the pathogenesis of some neurodegenerative disorders. The concept will be tested in cMyBP-Cmut/+ mice, which carry a mutation leading to a truncated cMyBP-C. The material and methods developed in the project are at the forefront of progress (targeted transgenesis, recombinant adenovirus, proteasome reporter mice, RNA interference, 3D-engineered heart tissue (inve nted and patented by T. Eschenhagen), echocardiography, Millar tip catheter, sarcomere length measurements, osmotic minipumps, confocal and electronic microscopy, transcriptome and proteome analysis).
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.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering control systems
- natural sciences chemical sciences inorganic chemistry alkaline earth metals
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine cardiology
- natural sciences chemical sciences organic chemistry amines
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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.
FP6-2002-MOBILITY-8
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
HAMBURG
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.