Molecular mechanisms evolutionary impacts and applications of prokaryotic epige...
Molecular mechanisms evolutionary impacts and applications of prokaryotic epigenetic targeted immune systems
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 biotec...
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Información proyecto EPICut
Duración del proyecto: 73 meses
Fecha Inicio: 2018-06-08
Fecha Fin: 2024-07-31
Líder del proyecto
UNIVERSITY OF BRISTOL
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
2M€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
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.