Improving bacteriophage efficacy in gut systems through transcriptomic and metagenomic analysis of the effect of novel synthetic biology-generated phage therapies

Streptococcus suis is a pig pathobiont that is almost ubiquitously carried in the nasopharynx and is a significant international animal welfare and economic burden in the pig industry.

This PhD is part of an international consortium involving partners from the US, Ireland and UK who aim to develop innovative and effective next-generation bacteriophage therapy solutions to specifically target S. suis in pigs. 

This project will utilise cutting edge DNA sequencing and computational analyses technologies to characterise both the transcriptional response of S. suis and the whole pig gut microbiome to the application of phage therapies generated through synthetic biology approaches.

This knowledge will allow us to design phages that are capable of circumventing resistance systems while minimising off target effects, thereby improving the success rate of phage cocktails in this and other gut systems.

The long-term goals of the project are to improve animal welfare and farm sustainability and to ultimately benefit consumer health. The project involves an international team of specialists from the US, Ireland and Northern Ireland to develop novel approaches to eradicate microbial pathogens in farm animals.

The overarching hypothesis is that delivery of engineered phages, or phage-products, will significantly reduce infection by the pathobiont Streptococcus suis in pigs.

Streptococcus suis is almost ubiquitously carried in the nasopharynx of pigs and is most commonly associated with a previous intestinal or respiratory infection, leading to S. suis-mediated meningitis, polyarthritis, septicaemia, pneumonia and endocarditis. Therefore, S. suis infections are a significant international animal welfare and economic burden in the pig industry.

This project is expected to yield innovative and effective phage therapy solutions to specifically target S. suis in pigs using a rational design approach to generate and test novel phage cocktails. This design will allow the phages in the cocktail to kill a wide range of infectious S. suis strains while circumventing bacterial-mediated phage resistance, a key roadblock to the use of phage therapy (PT).

This project addresses the vital topics of antibiotic usage in animal husbandry and worldwide antimicrobial resistance (AMR) in the context of veterinary care of pig welfare and the associated protection of the food chain.

The work carried out by this PhD project at Queen’s University Belfast will utilise cutting edge DNA sequencing and computational analyses developed at the Creevey lab to characterise both the transcriptional response of S. suis and the whole pig gut microbiome to the application of phage therapies generated through synthetic biology approaches.

This knowledge will allow us to design phages that are capable of circumventing resistance systems while minimising off target effects, thereby improving the success rate of phage cocktails in this and other gut systems.

More information about the project can be found in the Irish government announcement of the award here: https://tinyurl.com/Phage-suas and about other research in the Creevey lab at: http://creeveylab.org.

Supervisors: Professor Chris Creevey (Queen's University School of Biological Sciences), Dr Timofey Skvortsov (School of Pharmacy), and Professor Sharon Huws (School of Biological Sciences).

Start Date: As soon as possible (summer 2022 at latest)

Duration: 4 years

Specific skills required: Desirable skills include a background in microbiology, bioinformatics or computational biology, but training will be provided as necessary during the project. 

Anticipated Interview Date: Mid-February 2022