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Unwanted Invaders or Welcomed Guests: Impact of Prophage Integration Sites on Host Genomic Integrity and Evolution

Project description

Uncovering new roles for phages in genome editing

Bacteriophages inhabit over two-thirds of bacterial genomes, accounting for about 10 % of their DNA. They can integrate into host genes during lysogeny, influencing bacterial development and microbial communities such as the human gut microbiome. However, the evolutionary mechanisms behind phage integration and its regulatory effects remain unclear. In this context, the EU-funded PHAGE_ATTACH project will study how specific phage integrations affect host-phage interactions using bioinformatics and a new prophage database. Focusing on Bacillus subtilis, it will examine integrase specificity and its effects on phage-host fitness through engineered phages and imaging, aiming to reveal new phage roles in genome editing and deepen understanding of phage-bacteria coevolution.

Objective

Bacteriophages are found in over two-thirds of sequenced bacterial genomes, with phage DNA making up an estimated 10% of these genomes. Recent studies suggest that phage DNA integration, during so called lysogeny, can lead to interactions with bacterial hosts that are more complex than once thought. There are phages which very specifically and reversibly integrate into host genes, modulating host development. Altering bacterial behaviours can have detrimental consequences in microbial communities, such as those found in the human gut. However, it is unclear how specific phage integration mechanisms evolve, or if integration specificity influences regulation during lysogeny. I hypothesise that phage integration components are a key factor in phage-host interactions, with attachment sites (att) and phage integrases under strong evolutionary pressure. This project's goal is to examine the consequences of specific phage integration for the host and for the phage and to understand how integration components are directed by evolution. This will be fulfilled via three research objectives: 1) bioinformatics analysis of phage integration components, capitalizing on newly built prophage database and focusing on conservation of host att genes and phage integrases; 2) investigation of the effects of integrase specificity on phage-host interactions and fitness via combining engineered phages and trackable host with high-throughput imaging and RNA sequencing. 3) testing the long-term effect of specific att sites on host genome evolution in ecological context to Bacillus subtilis was selected as the model host due to its tractability, biotechnological importance, and susceptibility to phages with highly specific integrases. Understanding the impacts of phage integration specificity and its evolution will reveal new phage roles in host genome editing and gene transfer, improve our knowledge of phage-bacteria coevolution and it will pave new ways to engineering of bacterial genomes.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-WIDERA-2024-TALENTS-02

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Coordinator

UNIVERZA V LJUBLJANI
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 182 717,52
Address
KONGRESNI TRG 12
1000 Ljubljana
Slovenia

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Region
Slovenija Zahodna Slovenija Osrednjeslovenska
Activity type
Higher or Secondary Education Establishments
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Total cost

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