Project description DEENESFRITPL Investigating novel molecular anti-epileptic treatments MicroRNAs are non-coding RNAs with a key regulatory function on protein expression. Specific microRNAs have been associated with epilepsy, and their inhibition with antisense molecules known as antagomirs has shown promising anti-seizure results in animal models. The EU-funded EpimiRTherapy project focusses on the targeting of microRNA-134 as an anti-epileptic treatment. Researchers will use surgically resected human tissue to test the biophysical and transcriptional changes following application of microRNA-134 antagomirs, shedding light on the underlying mechanism. Combined with modelling approaches, the project's results have great translational potential and will pave the way for novel anti-epileptic therapies. Show the project objective Hide the project objective Objective 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. Fields of science medical and health sciencesbasic medicineneurologyepilepsynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator ROYAL COLLEGE OF SURGEONS IN IRELAND Net EU contribution € 184 590,72 Address ST STEPHEN'S GREEN 123 2 Dublin Ireland See on map Region Ireland Northern and Western Border Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 184 590,72
