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EPICut SIGNED

Molecular mechanisms, evolutionary impacts and applications of prokaryotic epigenetic-targeted immune systems

Total Cost €

EC-Contrib. €

Partnership

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EPICut project word cloud

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

coevolution eukaryotic resist dna prokaryotic phage influences evolutionary interdisciplinary methylation epigenome mechanisms horizontal genetic viruses mapping led nucleoprotein unravel interactions biophysical epigenetics enzymes base structure defence spread population glucosylation individual tools link cas9 reengineering enzyme little bacterial virulence gene editing markers crispr vital infection viral molecular biotechnology community single deeper resistance transfer mechanistic immunity molecule ecology bacteriophages immune phenotypes combines modified covalently function full bacteria rm true revolutions hydroxymethylation communities evolution secondly restriction firstly engineering modification antimicrobial sequencing

Project "EPICut" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITY OF BRISTOL Organization address address: BEACON HOUSE QUEENS ROAD city: BRISTOL postcode: BS8 1QU website: www.bristol.ac.uk 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	United Kingdom [UK]
Total cost	2˙196˙413 €
EC max contribution	2˙196˙413 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2017-ADG
Funding Scheme	ERC-ADG
Starting year	2018
Duration (year-month-day)	from 2018-08-01 to 2023-07-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITY OF BRISTOL UNIVERSITY OF BRISTOL Organization address address: BEACON HOUSE QUEENS ROAD city: BRISTOL postcode: BS8 1QU website: www.bristol.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (BRISTOL)	coordinator	1˙758˙623.00
2	THE UNIVERSITY OF EXETER THE UNIVERSITY OF EXETER Organization address address: THE QUEEN'S DRIVE NORTHCOTE HOUSE city: EXETER postcode: EX4 4QJ website: www.ex.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (EXETER)	participant	437˙790.00

Map

Project objective

Interactions between bacteria and their viruses (bacteriophages) have led to the evolution of a wide range of bacterial mechanisms to resist viral infection. The exploitation of such systems has produced true revolutions in biotechnology; firstly, the restriction-modification (RM) enzymes for genetic engineering, and secondly, CRISPR-Cas9 for gene editing. This project aims to unravel the mechanisms and consequences of prokaryotic immune systems that target covalently-modified DNA, such as base methylation, hydroxymethylation and glucosylation. Very little is known about these Type IV restriction enzymes at a mechanistic level, or about their importance to the coevolution of prokaryotic-phage communities. I propose a unique interdisciplinary approach that combines biophysical and single-molecule analysis of enzyme function, nucleoprotein structure determination, prokaryotic evolutionary ecology, and epigenome sequencing, to link the molecular mechanisms of prokaryotic defence to individual, population and community-level phenotypes. This knowledge is vital to a full understanding of how bacterial immunity influences horizontal gene transfer, including the spread of virulence or antimicrobial resistance. In addition, a deeper analysis of enzyme function will support our reengineering of these systems to produce improved restriction enzyme tools for the mapping of eukaryotic epigenetics markers.

Publications

List of publications.
year	authors and title	journal	last update
2019	Kara van Aelst, Carlos MartÃnez-Santiago, Stephen Cross, Mark Szczelkun The Effect of DNA Topology on Observed Rates of R-Loop Formation and DNA Strand Cleavage by CRISPR Cas12a published pages: 169, ISSN: 2073-4425, DOI: 10.3390/genes10020169	Genes 10/2	2020-03-23

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