Objectives and attending results The project aim by screening libraries of icefish heart transcriptome to find significant signalling pathways inducing the hypertrophy. By studying these pathways, we can find small molecules that can block or modify the disease in culture models, using ZF and later human cardiomyocytes derived from pluripotent stem cells (hc-iPSCs).
The hc-iPSCs carry mutations that cause familial HCM and reproduce hallmark features of myopathy and arrhythmia that make these cells ideal as screenable models The The hc-iPSCs will aggregate in 2D/3D-cardiospheres model and, finally, in organoids that display the disorder traits. The chemical and functional genomics projects have proposed several small molecules to test. The spheroid/organoid models, showing the icefish gene modifications as we have learned will permit the evaluation of drug candidates to reverse the pathology or study the effects in miniaturised hearts growing in a culture plate. A significant focus for the future will be to use the know-how from icefish to iPSC disease/ZF-disease models to refine the structure of compounds to remove cardiomyopathy and proarrhythmic disabilities.
• Understand the cellular pathways/genes implied in the physiological hypertrophy adaptation in icefish.
Find genes give the icefish heart the ability not to go towards pathology.
• Reproduce these pathways in transductional models such as the ex-vivo culture of cells from ZF and
consequently in humans cardiac(iPSCs/spheroids/organoids) to study the cardiac hypertrophy to
evaluate and study the physio pathological molecular mechanisms leading hypertrophy.
• Find the possible molecules target to and new potential molecules that can block cardiac hypertrophy
in icefish and in human organoid model
• Transfer and disseminate the knowledge to the scientific community and social media
SENSOWORKS, Italia
BRENG, Italia
ROMA TRE, Italia
LINK UNIVERSITY, Italia
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