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

Total Cost €


EC-Contrib. €






Project "EPICut" data sheet

The following table provides information about the project.


Organization address
postcode: BS8 1QU

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


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF BRISTOL UK (BRISTOL) coordinator 1˙758˙623.00
2    THE UNIVERSITY OF EXETER UK (EXETER) participant 437˙790.00


 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.


year authors and title journal last update
List of publications.
2019 Kara van Aelst, Carlos Martínez-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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