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Translational and posttranslational control of truncated titin proteins in cardiomyocytes from dilated cardiomyopathy patients (A08(B03))

Subject Area Cardiology, Angiology
Term since 2012
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 193793266
 
Up to 25% of patients with dilated cardiomyopathy have truncating mutations in the TTN gene (TTNtv). The pathomechanism of TTNtv is not well understood. In A08, we hypothesize that the pathophenotypic diversity of TTNtv patients has to do with a variable translational readthrough of TTNtv mRNA, as well as with varying but progressively increasing levels of truncated titin protein due to inefficient protein quality control later in life. We will use human heart tissues, iPSC-derived cardiomyocytes and engineered heart muscle to quantify and modulate TTNtv protein expression and aggregation, and to study their effects on cardiomyocyte structure and function. Our data will establish the link between TTNtv proteins and heart failure progression and uncover novel treatment perspectives.
DFG Programme Collaborative Research Centres
Applicant Institution Georg-August-Universität Göttingen
 
 

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