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Bacteriophages

Primary Supervisor: Dr Andrew Millard, Department of Genetics and Genome Biology

Secondary Supervisor: Professor Martha Clokie, Department of Genetics and Genome Biology

PhD project title: Bacteriophages

University of Registration: University of Leicester

Project outline:

Bacteriophages are the most abundant entity on the planet and are known to drive the evolution of their bacterial hosts. Bacteriophages are known to convert harmless bacteria into pathogens by a process known as phage conversion. Bacteriophages are also mediators of horizontal gene transfer, providing a mechanism for DNA to be transferred between bacterial hosts via generalised and specialised transduction. Furthermore, phages can increase the severity of bacterial infections by acting as decoys to the immune system. With the immune system fighting the viral infection rather than their bacterial hosts, allowing the bacterial infection to be maintained.

In addition to the possible detrimental effects of phages on human health (eg spread of antibiotic resistance genes, increased bacterial virulence), they also hold hope as novel source of antibiotics. The potential of bacteriophages to be used a therapeutics against pathogens is becoming increasingly recognised as is the use of phages to remodel the microbiome.

Despite the importance of bacteriophages, most of what we know about bacteriophages is based on a relatively small number of bacterial-phage host systems. Approximately 60% of phages that have been sequenced have been isolated on just 12 different genera of bacteria. These genera tend to be representative of human pathogens eg Salmonella sp , Myobacterium sp Shigella sp . However, there is a dearth of knowledge on the diversity of phages that infect the commensal bacteria found in the human gut. Furthermore, there is virtually no model phage-host model systems for commensal gut bacteria.

To fully understand the role of phages it is necessary to develop phage-host systems so that hypotheses may be tested.

 Objectives

  • Predict prophages in recently published biobank of human gut bacteria
  • Induce and experimentally confirm prophages in small number of important gut bacteria
  • Isolate lytic bacteriophage against a range of commensal human gut bacteria
  • Investigate the role of both lytic and temperate phages on commensal gut bacteria

References:

  1. Forster, S.C.; Kumar, N.; Anonye, B.O.; Almeida, A.; Viciani, E.; Stares, M.D.; Dunn, M.; Mkandawire, T.T.; Zhu, A.; Shao, Y.; et al. A human gut bacterial genome and culture collection for improved metagenomic analyses. Biotechnol. 2019.
  2. Poyet, M.; Groussin, M.; Gibbons, S.M.; Avila-Pacheco, J.; Jiang, X.; Kearney, S.M.; Perrotta, A.R.; Berdy, B.; Zhao, S.; Lieberman, T.D.; et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Med. 2019.

BBSRC Strategic Research Priority: Integrated Understanding of Health: Microbiology

Techniques that will be undertaken during the project:

  • Phage isolation
  • Prophage/lytic phage sequencing via nanopore
  • Prophage prediction through DeepLearning methodology
  • Bioinformatic analysis of prophages

Contact: Dr Andrew Millard, University of Leicester