Close
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听 in AMR, the development of new antimicrobials has been stifled. Approaches and potential PhD听projects to develop new antimicrobial therapies include:
- Improved (pre-clinical) assessment of听combination therapies, using multiple antimicrobials together to increase efficacy and prevent听emergence of resistance;
- Bacteriophage-based therapy, use of (natural and engineered) viruses听 that infect bacteria or use of the viral enzymes as antimicrobials;
- Repurposing and reengeering of听existing drugs;
- Discovery and characterisation of new antimicrobials and antimicrobial delivery听vehicles.
On the other hand, vaccines are essential tools to prevent infectious diseases by听stimulating the immune system to produce a protective response against specific pathogens.听Vaccine-oriented projects can focus on, e.g.
- Discovery, using advanced physical-sciences听methods to identify potential antigens or developing new formulations of weakened forms of the听pathogen that can induce an immune response without causing disease; or on
- Process听engineering required for increasing the supply of existing or vaccines in development.
Research Theme Contacts:
Prof Joanne Santini and Prof Bart Hoogenboom听
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听combination with other antimicrobials. Examples of such enzymes are endolysins that degrade听bacterial cell walls and depolymerases that degrade bacterial capsules. These enzymes have听multiple advantages over the use of the phages that they originate from: they cover broader host听ranges, can be produced at scale as recombinant proteins and the emergence of bacterial听resistance is rare. In this project, we will discover and engineer such depolymerases as听antimicrobials. A bioinformatic approach will be used to detect depolymerases in phages that听target the AMR pathogen Klebsiella pneumoniae, an opportunistic and hospital acquired听pathogen which causes a variety of diseases (e.g., pneumonia, sepsis, UTIs etc). We will use a听machine-learning approach to design de novo depolymerases with expanded host range against听different capsule types. These new enzymes will be produced recombinantly, purified and tested听in vitro in combination with antibiotics against a variety of AMR K. pneumoniae clinical isolates.听
External Engagement
Production of a chosen recombinant depolymerase with optimised and听final formulation determined with external partner听
Project Impact
New phage enzyme screening platform; development of novel antibacterials.
Student Career Destination
Pharmaceutical industry, academia.
听