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        The design of fluorescent cobalt antifungals for targeting antimicrobial resistance
 
        Secondary Supervisor(s): Professor Peter Sadler, Dr Stefan Bidula
 
        University of Registration: University of Warwick
 
        BBSRC Research Themes:
 
         
        Project Outline
 
        The global rise of antimicrobial resistance (AMR) poses a major threat to public health, with fungal pathogens increasingly contributing to life-threatening, drug-resistant infections. The emergence of multi-drug-resistant species such as Candida auris and Aspergillus fumigatus highlights the urgent need for novel antifungal agents with distinct mechanisms of action that can overcome existing resistance.
 
        Transition metal complexes, particularly those based on cobalt, have gained attention due to their unique bioactivities and potential to bypass classical resistance mechanisms. Our team has recently demonstrated some cobalt complexes which show promising antifungal activity against A. fumigatus and which potentially have novel mechanisms of action. Building on this foundation, this project will focus on the development of fluorescent cobalt-based complexes to serve both as therapeutic candidates and mechanistic probes.
 
        The scientific rationale lies in cobalt's redox versatility, ability to form stable but biologically active complexes, and its known effects on fungal cell metabolism and oxidative stress pathways. By incorporating fluorescent ligands, these complexes can provide new insights into fungal uptake, intracellular localisation, and the mechanism of action.
 
        The key objectives are to:
 
        (1) synthesise and characterise a diverse library of fluorescent cobalt complexes;
 
        (2) evaluate their antifungal activity in vitro against clinically relevant fungal strains;
 
        (3) use fluorescence-based imaging and biochemical assays to investigate uptake, intracellular distribution, and potential for resistance evasion, supported by transcriptomic and proteomic analyses.
 
        This interdisciplinary project combines synthetic chemistry, microbiology, and molecular biology to develop innovative antifungal strategies and address a critical gap in tackling fungal AMR.