Descripción del proyecto
Investigación de tratamientos antiepilépticos moleculares novedosos
Los microARN son ARN no codificantes con una función reguladora clave de la expresión proteica. Se han relacionado unos microARN específicos con la epilepsia, y su inhibición con unas moléculas antisentido llamadas antagomires ha mostrado unos resultados anticonvulsivos prometedores en modelos animales. El proyecto financiado con fondos europeos EpimiRTherapy se centra en el microARN-134 como tratamiento antiepiléptico. Los investigadores del proyecto emplearán tejidos humanos extirpados quirúrgicamente para probar los cambios biofísicos y transcripcionales tras la aplicación de antagomires de microARN-134, de forma que arrojarán luz sobre el mecanismo subyacente. Los resultados del proyecto, combinados con métodos de modelización, presentan un gran potencial de traslación y allanarán el camino a nuevas terapias antiepilépticas.
Objetivo
The overall research aim of EpimiRTherapy is to elucidate the mechanism of a novel disease-modifying therapy for epilepsy at single cell resolution in the human brain. MicroRNAs are short non-coding RNAs which regulate protein levels in the brain. Certain microRNAs are strongly associated with epilepsy and their knockdown, using antisense molecules called ‘antagomirs’, has anti-seizure effects in rodents. Antagomir targeting microRNA-134 (ant-134) is a particularly promising disease-modifying treatment for epilepsy, which could meet an urgent clinical need. However, antagomirs to treat neurological disease have never been tested in humans due to limited translational evidence. EpimiRTherapy, for the first time, fills this gap: I will use state-of-the-art techniques to produce human brain slices from tissue surgically resected during temporal lobectomies for epilepsy. I will use a combination of molecular techniques (acquired at the host lab in RCSI and through secondment to ICL) and electrophysiology, my core expertise, to determine the impact of ant-134 on the biophysical and transcriptional landscapes of human tissue and a network and single neuron level. This will be complemented with cutting edge systems modelling and imaging techniques acquired through collaborations. This fellowship, through advanced interdisciplinary and intersectoral training, will serve as a launchpad for reaching a position of professional independence and maturity, whilst at the same time facilitating a transfer of knowledge between myself, the host and the collaborators, by bringing cutting edge electrophysiology and human tissue processing techniques to RCSI and addressing an urgent and unmet clinical need for novel epilepsy treatments.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
2 Dublin
Irlanda