Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression, particularly in processes important to cardiac development and repair. Recent studies show that specific lncRNAs modulate cardiomyocyte cell cycle activity, influencing the heart’s limited capacity for regeneration after injury. This project aims to identify and functionally characterise lncRNAs that regulate cardiomyocyte proliferation and heart regeneration.
This project focusses on a series of small RNAs and lncRNAs that we have identified over the last years through a few systematic high-throughput screenings for their capacity of regulating cardiomyocyte replication.
Target discoveryIn depth
Our goal is to identify novel long RNAs (lncRNAs) that regulate heart muscle cell growth. We utilise bioinformatic analysis, high throughput screening assays, characterisation of molecular mechanisms, long RNA manipulation in a lab in vivo model of heart attack and evaluation both in human cardiac cells derived from stem cells and living human heart tissue.
To achieve this, we are going to use very deep RNA sequencing and transcriptome reassembly, together with comprehensive bioinformatic and machine learning approaches. Single cell RNA sequencing will help identify their expression patterns in relevant cardiac cell types. To uncover underlying mechanisms, RNA pulldown coupled with mass spectrometry will be utilised to access the molecular mechanisms associated to IncRNA function, involving identification of the IncRNA protein interaction partners and apply GapmeR antisense oligonucleotides for targeted lncRNA knockdown in vitro and in vivo.
Promising lncRNAs will then be tested in human ESC-derived cardiomyocytes and human living myocardial tissues, enabling assessment of translational therapeutic potential. Finally, we are going to examine cardiomyocyte responses using spatial transcriptomics in human heart tissues.