Objective
Laminopathies are inherited human disorders, including muscular dystrophy, cardiomyopathy, lipodystrophy, insulin-resistance, diabetes, and premature aging, which are linked to mutations in genes encoding nuclear envelope proteins, such as A-type lamins (LMNA) and lamin-binding proteins (EMD, LBR, LAP2). Laminopathies are clinically manifested after birth, progressively develop during childhood, and often lead to early death. Efficient therapies have been hampered by the lack of understanding the molecular mechanisms causing the disorders. We will test various disease hypotheses, identify drug targets, and screen drugs for therapeutic interventions. Structural biologists will investigate how disease-causing mutations in A-type lamins or in one of their prominent binding partners LAP2alpha affect atomic structure, interactions, and assembly properties of lamins, which may reduce stress resistance in patient cells. Using patient cells and animal models (mouse, C. elegans) that either lack A-type lamins or LAP2alpha, or express disease variants, we will test how mutations or loss of these proteins affect chromatin organization, gene expression, and differentiation of adult muscle- and adipose stem cells.
Differentiation will be studied ex vivo in cell culture, focusing on the molecular functions of A-type lamins and LAP2alpha in differentiation-linked pathways, and in vivo in animal models analyzing muscle regeneration after stress, injury, or aging. Data obtained in these systems as well as chemical compound screening using the zebrafish model system will identify potential drug targets and drugs for testing in animal disease models and for potential therapeutic intervention. Furthermore, we will extend and evaluate clinical trials on the treatment of lipodystrophy-type laminopathy patients with drugs that target the adipocyte differentiation pathway, and develop theranostic tests for the validation of therapies.
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 neurology muscular dystrophies
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology homeostasis
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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.
FP6-2004-LIFESCIHEALTH-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
VIENNA
Austria
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.