The Professor Tony Maxwell lab investigates the structure and mechanism of DNA topoisomerases and associated proteins, to further our understanding of key biological processes in which they are involved, and to harness this knowledge for the development of therapeutic agents, specifically antibiotics.
This work is carried out within the Molecules for Nature Institute Strategic Programme, under Theme 2: Biological Context.
DNA topoisomerases are vitally important enzymes involved in the control of the topological state of DNA. Their major biological functions are in DNA replication, transcription and the control of gene expression. Topoisomerases provide fascinating systems for studying DNA-protein interactions and energy coupling in biological systems. Their study also has clinical relevance from the standpoint of antibacterial and anti-tumour drugs.
DNA gyrase, the enzyme from bacteria that carries out DNA supercoiling, is the target for clinically-important antibiotics, such as the fluoroquinolones.
In addition to gyrase, we are working on several related enzymes, including bacterial topoisomerase IV and the recently-discovered gyrases and topo VI enzymes from plants and plasmodial species. The work involves a wide range of methodologies including bacteriology, mutagenesis, protein engineering, plant molecular biology, enzymology, biophysical methods and X-ray crystallography.
The Maxwell lab are also working on insect gut bacteria as a way of exploring plant toxins to assess their usefulness as potential antibiotics. This involves analysing the microbiome of insects feeding on certain plants to obtain evidence of toxin compounds in the plant. They are currently investigating whether greater wax moth larvae (Galleria mellonella) can be used as a surrogate for investigating the human infant gut microbiome.
Germe T., Voros J., Jeannot F., Taillier T., Stavenger R. A., Bacqué E., Maxwell A., Bax B. D.A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance.Nucleic acids researchPublisher's version: 10.1093/nar/gky181
Evans-Roberts K. M., Mitchenall L. A., Wall M. K., Leroux J., Mylne J. S., Maxwell A.DNA Gyrase Is the Target for the Quinolone Drug Ciprofloxacin in Arabidopsis thaliana.Journal of Biological Chemistry (291)Publisher's version: 10.1074/jbc.M115.689554
Postdoc and PhD positions are frequently available. More information available on request.