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Using human tissue to translate microRNA-based therapies for epilepsy

Project description

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.

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.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

ROYAL COLLEGE OF SURGEONS IN IRELAND
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.

€ 184 590,72
Address
ST STEPHEN GREER 123
D02 YN77 DUBLIN 2
Ireland

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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.

€ 184 590,72
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