Description du projet
Examiner les nouveaux traitements anti-épileptiques moléculaires
Les microARN sont des ARN non-codants dotés d’une fonction régulatrice clé dans l’expression des protéines. Certains microARN ont été associés à l’épilepsie, et leur inhibition avec des molécules antisens connues sous le nom d’antagomirs a montré des résultats anti-convulsions prometteurs dans les modèles animaux. Le projet EpimiRTherapy, financé par l’UE, s’intéresse au ciblage du microARN-134 comme traitement anti-épileptique. Les chercheurs utiliseront du tissu humain prélevé chirurgicalement pour tester les changements biophysiques et transcriptionnels survenus suite à l’application d’antagomirs de microARN-134, apportant un éclairage sur le mécanisme sous-jacent. Combinés à des approches de modélisation, les résultats du projet présentent un grand potentiel d’application et ouvriront la voie à de nouveaux traitements anti-épileptiques.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
2 Dublin
Irlande