Developing of a tool-kit of chemical probes for bioimaging of microbial virulence

The increasing emergence of multi-drug-resistant microorganisms has led the World Health Organisation to plead for action against antimicrobial resistance (AMR). In order to control the spread of infectious diseases, such as the current COVID-19 pandemic, and to improve standard of health, is critical that new classes of antimicrobial agents with novel mechanisms of action are developed. Poor efficacy and the rising of severe anti microbial resistance (AMR) to current antibiotics is now the main challenge to control and eradicate infectious diseases.
Pathogens like Mycobacterium tuberculosis (Mtb), Aspergillus fumigatus or Candida Albicans, use secreted virulence factors to challenge the normal immune response and avoid killing within host macrophages, thus establishing infection. However, the mechanisms of microbial survival and the host response to infection are still poorly understood.
This projects aims to develop specific and selective chemical ligands with fluorescent probes to target critical virulence factors to further study their role in pathogenesis using bio-imaging techniques. The knowledge gained from these investigations will advance our understanding of host-pathogen interactions and provide the basis for future new therapies to fight infections.

This project offers an exciting new approach to bioimaging critical pathogenesis processes in real life with potential applications for novel therapies. The project will involve a multidisciplinary approach with computational chemistry and structural biology (Tabernero), medicinal chemistry and organic synthesis (Butterworth), together with biochemical and imaging technologies. The collaborative nature of the project is a unique opportunity to engage in an interdisciplinary working environment and the complementary expertise of the supervisory team means that the student will have a much broader and rounded up training during the PhD.