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

Project description

Cardiac glial cells long non-coding RNAs as a target in the treatment of heart disease

Heart disease is the leading cause of death worldwide; understanding the regulation of cardiac neuronal function and remodelling could support advances in developing new therapies. Several long non-coding RNAs (lncRNAs) have been implicated in heart disease and thus represent attractive therapeutic targets given their cell type-specific expression. Glial cells (GCs) cover almost all neuronal cell surfaces and regulate neuronal function and remodelling. Preliminary research results show that cardiac GCs express many specific lncRNAs, deregulated in diseased conditions. The EU-funded GLIA-LNC project aims to identify cardiac GC lncRNAs with therapeutic potential. To achieve this, project work is focused on identifying the GC populations that mediate neuronal remodelling, the lncRNAs that determine identity and function of cardiac GCs, and the interaction partners regulating GC functions.

Objective

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 162 806,40
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 162 806,40
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