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

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.

Host institution

UNIVERSITY OF BRISTOL
Net EU contribution
€ 1 758 623,75
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom

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Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00

Beneficiaries (2)

UNIVERSITY OF BRISTOL
United Kingdom
Net EU contribution
€ 1 758 623,75
Address
Beacon House Queens Road
BS8 1QU Bristol

See on map

Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00
THE UNIVERSITY OF EXETER
United Kingdom
Net EU contribution
€ 437 790,00
Address
The Queen's Drive Northcote House
EX4 4QJ Exeter

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Region
South West (England) Devon Devon CC
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00