Project description
Recapitulating cardiac disease in vitro
Creating functional models of the human myocardium is central to studying its physiology and dissecting the pathological mechanisms of cardiovascular diseases. However, the complex structure and function of the human heart has posed a significant challenge to the establishment of robust models. Funded by the Marie Skłodowska-Curie Actions programme, the ACCURACY project will employ an in vitro cardiac model based on human induced pluripotent stem cells (hiPSC). The idea is to study the pathogenesis of lamin cardiomyopathy, a rare genetic disorder caused by mutations in the genes that encode structural proteins of the nucleus. Moreover, the project will pave the way towards new treatment options.
Objective
Lamin A/C cardiomyopathy (LMNA-CM) is a rare genetic disorder caused by mutations in the nuclear lamin gene LMNA. Affected patients typically exhibit dilated cardiomyopathy and reduced life expectancy, due to sudden cardiac death or accelerated functional decay requiring the heart transplant. Intriguingly, carriers of the same LMNA mutation show a wide spectrum of genotype-phenotype discrepancy, however a clear mechanistical understanding remains elusive. Recently, the host laboratory has developed an innovative multicellular three-dimensional (3D) human induced pluripotent stem cells (hiPSC)-cardiac microtissue (MT) model where hiPSC-derived cardiomyocytes display post-natal maturation allowing more faithful investigation of normal and pathological cardiac physiology. I will leverage this model and combine it with my strong background in molecular and cellular cardiology to advance the understanding of LMNA-related pathologies. Specifically, I will use patient-derived hiPSC from two family members with a severe and less severe form of LMNA-CM and their isogenic controls to generate 3D MT models. Next, I plan to 1) characterize structural and functional properties and the transcriptome profile of multicellular LMNA MT models and their controls, 2) investigate cell-cell (cardiomyocytes, endothelial cells, cardiac fibroblasts and macrophages) interactions relevant to the disease development and progression, and 3) correct the identified molecular targets by pharmacological treatment or by CRISPR-mediated gene editing. The scientific, industrial and economic community will profit from this project twofold. First, I will establish a cost-effective model that provides better understanding of LMNA-CM pathogenesis, avoids cross-species variability and reduces the need for animal research and second, I will test the implementation of potential treatment options with the ambition to achieve a step forward in developing personalized therapeutic approach for the end users.
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 RNA transcriptomes
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
- medical and health sciences clinical medicine cardiology
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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)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
Funding Scheme
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2021-PF-01
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35122 Padova
Italy
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