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EpiMIRgen

A comprehensive analysis of microRNA-124 regulated gene networks and its role in epilepsy.

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

EpiMIRgen project word cloud

Explore the words cloud of the EpiMIRgen project. It provides you a very rough idea of what is the project "EpiMIRgen" about.

models function pleiotropic evidence data ectopically functional resected epigenomic regulation translatable demonstrates mouse rapid transgenic correct clip epilepsy mice molecules seq post network profiled profound aberrant underlies restitution human disease epileptic introduce regulator ribosomal epileptogenesis model obtaining microrna persisting effect regulated form culture networks nrsf spec hits neuronally gene profiling transcriptome expression energetics epigenetic hippocampus causes standard epileptogenic builds mir transcriptional calcium first maintaining overexpressing intervene ko disorder mirna proteomic preliminary mature master enriched treatment crispr disruption mass restore examine prevent neurons 124 live therapeutic modifiers imaging transcriptomic modify atac

Project "EpiMIRgen" data sheet

The following table provides information about the project.

Coordinator	ROYAL COLLEGE OF SURGEONS IN IRELAND Organization address address: Saint Stephen's Green 123 city: DUBLIN postcode: 2 website: www.rcsi.ie contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Ireland [IE]
Project website	https://sites.google.com/view/epimirgenh2020/
Total cost	187˙866 €
EC max contribution	187˙866 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2015
Funding Scheme	MSCA-IF-EF-RI
Starting year	2016
Duration (year-month-day)	from 2016-07-01 to 2018-06-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	ROYAL COLLEGE OF SURGEONS IN IRELAND ROYAL COLLEGE OF SURGEONS IN IRELAND Organization address address: Saint Stephen's Green 123 city: DUBLIN postcode: 2 website: www.rcsi.ie contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IE (DUBLIN)	coordinator	187˙866.00

Map

Project objective

Evidence is emerging that rapid, profound and persisting changes in gene expression regulation and post-transcriptional regulation underlies the epileptogenic process. The current proposal builds on preliminary data which demonstrates that rapid reduction of a microRNA; miR-124, causes increased expression and activity of NRSF, a master-regulator of epileptogenesis. The current proposal will build on this and investigate other gene networks regulated by miR-124 in neurons, by developing the first miR-124 KO mouse using CRISPR technology and a miR-124 overexpressing mouse. These transgenic mice will then be profiled at the epigenomic level using ATAC-Seq, the transcriptome level using HITS-CLIP and ribosomal profiling and the proteomic level using mass spec. This will be the first study to examine the pleiotropic role of miR-124 in mature neurons and identify gene networks regulated by this neuronally enriched miRNA. If miR-124 disruption causes aberrant activity of epigenetic modifiers including NRSF then we will test whether miR-124 restitution can restore correct gene expression networks and prevent or modify epileptogenesis in a mouse model of the disorder. Next we will determine whether data obtained in mouse models is translatable to the human form of the condition by obtaining and maintaining resected human epileptic hippocampus live in culture. We will ectopically introduce miR-124 and test the effect of miR-124 restitution on network activity and energetics using live-calcium imaging as well as the epigenomic and transcriptomic effects. Together this proposal represents the most in-depth analysis of miRNA function and will set the standard for future functional analyses of these molecules. Furthermore it has the potential to intervene in disease process and apply findings to a relevant human model providing a novel therapeutic target for the treatment of epilepsy.

Publications

List of publications.
year	authors and title	journal	last update
2018	Gary P. Brennan, David C. Henshall microRNAs in the pathophysiology of epilepsy published pages: 47-52, ISSN: 0304-3940, DOI: 10.1016/j.neulet.2017.01.017	Neuroscience Letters 667	2019-06-13
2017	Tobias Engel, Gary P. Brennan, Amaya Sanz-Rodriguez, Mariana Alves, Edward Beamer, Orla Watters, David C. Henshall, Eva M. Jimenez-Mateos A calcium-sensitive feed-forward loop regulating the expression of the ATP-gated purinergic P2X7 receptor via specificity protein 1 and microRNA-22 published pages: 255-266, ISSN: 0167-4889, DOI: 10.1016/j.bbamcr.2016.11.007	Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1864/2	2019-06-13

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The information about "EPIMIRGEN" are provided by the European Opendata Portal: CORDIS opendata.