Chemical Biology in Drug Discovery Laboratory
Lab head: Rachel Codd
Location: Blackburn Building, Camperdown
Our laboratory applies techniques in chemical biology to drug design, discovery, and pharmaceutics processing. Our chief interests lie in better understanding the mechanisms used by bacteria to acquire iron, from the level of siderophores, which are small-molecular-weight compounds produced by bacteria to sequester Fe(III), through to the cognate Fe(III)-siderophore recognition proteins, which are expressed at the bacterial cell surface. Bacterial iron uptake is significant in biomedicine, since:
- natural siderophores or siderophore mimics can be used to treat iron-overload disease and cancer; and
- molecules that antagonise iron uptake in both pathogenic and non-pathogenic bacteria are potential antibiotics.
To access these target molecules, and to discover new bacterial metabolites of biomedical interest, our laboratory uses approaches that traverse chemical proteomics, affinity chromatography using designer resins, metal-templated synthesis, semisynthesis and precursor directed biosynthesis.
Lab members: R Codd (head)
Capture of bleomycins from Streptomyces verticillus
Primary supervisor: Rachel Codd
Bleomycins are a family of metal-dependant glycopeptide-based DNA-cleaving antibiotics produced by Streptomyces verticillus, which are used in combination therapy for the treatment of Hodgkin’s disease, head and neck cancer, certain lymphomas and testicular cancer. Bleomycins have complex structures and cannot be synthesized. Bleomycins used in the clinic are isolated from fermentation. Our laboratory is using an affinity-based capture technique for expediting access to biomedically relevant bacterial secondary metabolites. In this project, you will apply this technique to capture molecules that model the metal-binding region of bleomycins as a prelude to capturing bleomycins direct from bacterial culture. A successful outcome to this project will provide a rapid and high yielding route to bleomycins using green technology that will have significant advantages above current processing approaches.