PhD by Research Programme (Infection and Immunity)

Associate Professor Kevin Pethe, LKCMedicine

Co-supervisor:

Associate Professor Eric Yap, LKCMedicine

Project Description:

Background: 

Bacteriophages are the most abundant biological systems on earth, outnumbering bacteria by a large number. Phages play a role in the ecology of most environments by impacting the cycling of organic matter and regulating bacterial population. As an example, it is estimated that 10–20% of the bacterial community is lysed daily by viruses, a critical mechanism to limit bacteria proliferation. Phages are also a key driving force that shape genetic diversity by accelerating the transfer of genetic material between bacteria by a mechanism known as transduction.

Phages being so numerous, it is not surprising to find them in our body. Their role in microbiota ecology is poorly understood, but phages probably modulate microbiota composition, indirectly impacting many aspects of human metabolism.

Shortly after their discovery 100 years ago, phage therapy was experimented to control bacteria infection. It is interesting to note that the earliest therapeutic phages were isolated from chicken feces, supporting the notion that endogenous phages could use as an alternative to antimicrobial agents.

The aim of this project is to explore alternate strategies to control the spread of multi-drug resistant bacteria and to explore the role of endogenous phages in the transmission of genetic material between pathogenic and commensal bacteria.

Proposed work: 
1. Isolation of phages from the human gut flora and the environment; with a focus on phages specific to opportunistic pathogens (e.g. Klebsiella pneumoniae, Acinetobacter baumanii, Staphylococcus aureus, Clostridium difficile). 
2. Metagenomics of phage present in gut microbiota (human and animals).
3. Selection of the most active phages, validation of their therapeutic potential in vitro (e.g. as biocides for environmental surfaces) and in animal models.
4. Study of the role of phages in the transmission of drug-resistant determinants (e.g. New Delhi Metallo-beta-lactamase-1 (NDM-1) or plasmid fragments) between opportunistic pathogens and commensal bacteria.

If you have questions regarding this project, please email the Principal Investigator, Associate Professor Kevin Pethe, at kevin.pethe@ntu.edu.sg.