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

Objetivo

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.

Palabras clave

Régimen de financiación

ERC-ADG - Advanced Grant

Institución de acogida

UNIVERSITY OF BRISTOL
Aportación neta de la UEn
€ 1 758 623,75
Dirección
BEACON HOUSE QUEENS ROAD
BS8 1QU Bristol
Reino Unido

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Región
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 758 623,75

Beneficiarios (2)