The non-coding genome in cardiac ageing and regeneration

Since the completion of the human genome project the number of protein-coding genes has been gradually corrected down to ~20,000 genes, or roughly the same number of genes found in the roundworm C. elegans. During the past decade, it became increasingly evident that the bigger part of our genome, which was considered ‘Junk DNA’, is actively transcribed into non-coding RNAs. Especially, in vertebrates ncRNAs are currently emerging as pivotal players in virtually all biological processes where they are believed to contribute significantly to biodiversity and disease susceptibility including cardiovascular ageing and disease. Our group is interested in identifying functional ncRNAs which play crucial roles in the processes of neonatal heart regeneration as well as cardiac ageing. Since telomere biology is directly associated with ageing and regeneration we are further interested in the link between ncRNAs and telomere dynamics. Our vision is the therapeutic exploitation of ncRNA and telomere biology aiming to enhance mammalian cardiomyocyte proliferation, thus boosting cardiac regeneration to combat heart disease.

 

Group members

  • Prof. Dr. Christian Bär, Group Leader (see CV)
  • Shambhabi Chatterjee, PhD, Postdoc, Junior Group Leader
  • Erika Hilbold, PhD, Postdoc
  • Jeannine Hoepfner, PhD, Postdoc
  • Anne Bührke, PhD, Postdoc
  • Hannah Hunkler, PhD, Postdoc
  • Anselm Derda, MD, Clinician scientist
  • Sarah Cushman, Postdoc
  • Malte Juchem, Postdoc
  • Elisa Mohr, PhD student
  • Jia Li Ye, PhD student
  • Anika Gietz, technician
  • Andrea Korte, technician
  • Isabelle Riedel, technician

Methodology:

  • telomere length analysis (Tel-qFISH, Tel-qPCR)
  • telomeric repeat amplification protocol (TRAP assay)
  • RNA pulldown
  • RNA FISH
  • IncRNA library approaches (shRNA, CRISPR/Cas9)
  • genome editing (CRISPR/Cas9)
  • hiPSC generation, culture and cardiomyocyte differentiation
  • AAV-mediated gene expression (gene therapy)
  • hypoxia stimulation in vitro
  • antisense-mediated gene and ncRNA knockdown
  • in vitro and in vivo imaging (fluorescence (confocal) microscopy, IVIS)
  • disease mouse models
  • LAD ligation in neonatal and adult mice
  • mouse and rat cardiac cell fractionation
  • histopathology analysis

Projects:

1.      The role of lncRNAs and telomerase in cardiomyocyte function and cardiac regeneration in vitro and in vivo.

2.      Contribution of lncRNAs to cardiac ageing in mice and humans.

3.      Leukocyte telomere length and circulating RNAs as biomarkers for cardiovascular disease.

4.      LncRNAs as regulators of cellular proliferation.

5.     CircRNAs in cardiac disease.

6.     IPSC-based in vitro disease modelling (Fabry disease).

7.     CRISPR/Cas9-based library approaches for the identification of cardioprotective lncRNAs.