Long non-coding RNAs that regulate glial cell function in the diseased heart

Despite progress in acute treatment, heart disease remains the leading cause of death worldwide. Current treatments fail to prevent cellular disease processes or to promote tissue recovery after cardiac events.

Since cardiac disease is accompanied by dramatic changes in neuronal integrity, understanding of the factors that regulate cardiac neuronal function and remodelling could facilitate development of novel therapies for heart disease.Long non-coding RNAs (lncRNAs) represent attractive therapeutic targets due to their highly cell type specific expression and function.

Several lncRNAs were indeed shown to be causally involved in heart disease, but the vast majority of cardiac lncRNAs still await characterization.The heart is densely innervated by nerve fibres which regulate cardiac function on a beat-to-beat basis.

In turn, glial cells (GCs), which cover almost all neuronal cell surfaces, locally regulate neuronal function and remodelling.

While neuronal function and remodelling play a key role in heart disease, little is known about the role of cardiac GCs and their lncRNAs.My preliminary data suggest that cardiac GCs express many cell type specific lncRNAs that are deregulated in diseased conditions.

To identify cardiac GC lncRNAs with therapeutic potential, I will 1) characterize cardiac GC populations that mediate neuronal remodelling in the heart, 2) identify conserved lncRNAs that determine cardiac GC identity and function, and 3) characterize their interaction partners and their ability to regulate key GC functions.These objectives will be addressed using cutting-edge techniques, including single cell sequencing and multiplexed CRISPR interference, during a fellowship at the research group of Prof.

Engelhardt in Munich. To do so, I will receive extensive interdisciplinary training and benefit from world-class research infrastructure. Finally, proactive dissemination and communication will ensure that this fellowship benefits society as a whole.