Novel Therapies

The Novel Therapies theme of the CDT will focus on Increasing the supply and development of antimicrobials & vaccines

Antimicrobials are drugs used to treat bacterial, viral, fungal and parasitic infections. Amid the rise  in AMR, the development of new antimicrobials has been stifled. Approaches and potential PhD projects to develop new antimicrobial therapies include:

• Improved (pre-clinical) assessment of combination therapies, using multiple antimicrobials together to increase efficacy and prevent emergence of resistance;
• Bacteriophage-based therapy, use of (natural and engineered) viruses  that infect bacteria or use of the viral enzymes as antimicrobials;
• Repurposing and reengeering of existing drugs;
• Discovery and characterisation of new antimicrobials and antimicrobial delivery vehicles.

On the other hand, vaccines are essential tools to prevent infectious diseases by stimulating the immune system to produce a protective response against specific pathogens. Vaccine-oriented projects can focus on, e.g.

• Discovery, using advanced physical-sciences methods to identify potential antigens or developing new formulations of weakened forms of the pathogen that can induce an immune response without causing disease; or on
• Process engineering required for increasing the supply of existing or vaccines in development.

Research Theme Contacts:

Prof Joanne Santini and Prof Bart Hoogenboom 

Example PhD Project

Engineering novel bacteriophage-based antimicrobials.

Student UG/PGT background

Physical sciences, engineering or life sciences.

Project Details:

Bacteriophage enzymes can be used as therapeutics either alone or in combination with other antimicrobials. Examples of such enzymes are endolysins that degrade bacterial cell walls and depolymerases that degrade bacterial capsules. These enzymes have multiple advantages over the use of the phages that they originate from: they cover broader host ranges, can be produced at scale as recombinant proteins and the emergence of bacterial resistance is rare. In this project, we will discover and engineer such depolymerases as antimicrobials. A bioinformatic approach will be used to detect depolymerases in phages that target the AMR pathogen Klebsiella pneumoniae, an opportunistic and hospital acquired pathogen which causes a variety of diseases (e.g., pneumonia, sepsis, UTIs etc). We will use a machine-learning approach to design de novo depolymerases with expanded host range against different capsule types. These new enzymes will be produced recombinantly, purified and tested in vitro in combination with antibiotics against a variety of AMR K. pneumoniae clinical isolates. 

External Engagement

Production of a chosen recombinant depolymerase with optimised and final formulation determined with external partner 

Project Impact

New phage enzyme screening platform; development of novel antibacterials.

Student Career Destination

Pharmaceutical industry, academia.