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

Descripción del proyecto

El ARN no codificante de cadena larga de las células gliales cardíacas como diana en el tratamiento de las cardiopatías

Las cardiopatías son la principal causa de muerte en todo el mundo. Entender la regulación y el remodelado de la función neuronal cardíaca podría contribuir a avances en el desarrollo de nuevos tratamientos. Se han relacionado varios ARN no codificantes de cadena larga (ARNncl, o lncRNA por sus siglas en inglés) con las cardiopatías, por lo que, dada su expresión específica del tipo celular, constituyen unas dianas terapéuticas atractivas. Las células gliales cubren casi todas las superficies de las neuronas y regulan la función y el remodelado neuronal. Los resultados preliminares muestran que las células gliales cardíacas expresan muchos ARNncl específicos, desregulados en caso de enfermedad. El proyecto financiado con fondos europeos GLIA-LNC pretende identificar ARNncl de células gliales cardíacas con potencial terapéutico. Para lograrlo, el trabajo del proyecto se centra en identificar las poblaciones de células gliales que median en el remodelado neuronal, los ARNncl que determinan la identidad y función de las células gliales cardíacas, y los socios de interacción que regulan las funciones de las células gliales.

Objetivo

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.