My research career can be broadly summed up as an interest in global regulatory mechanisms that allow microorganisms to respond to the environment. My primary approach is usually genetic but once hypotheses have been generated I will use whatever techniques are approriate.
Induction of carotenoid biosynthesis in Myxococcus Xanthus . We have developed a model of the molecular basis of blue-light induction of gene expression in this bacterium. It involves a sigma factor, a membrane-bound light-sensitive anti-sigma factor; a repressor and a novel anti-repressor. Currently we have a grant to study the nature of the repressor/anti-repressor interaction and we are close to reconstructing the system in Escherichia coli. Control of primary and secondary metabolism in Streptomyces coelicolor A3(2). The Gram-positive Streptomyces are responsible for the production of 53% of all known antibiotics. I am the world expert on Streptomyces primary metabolism and have shown that anabolism is not regulated as in other bacteria. We have discovered a bifunctional enzyme with a role in tryptophan and histidine biosynthesis. We have also demonstrated that enzymes used in isoleucine/valine synthesis are also used in proline biosynthesis. This has provided important insights into enzyme evolution as well as a more complete understanding of streptomycete primary metabolism.
We currently have a SysMo grant to study the alternative mechanisms of anaplerosis in streptomycetes. Characterisation of novel pathogenicity determinants in the Gram-positive bacterium Listeria monocytogenes. Listeria monocytogenes is the causative agent of the deadly, food-borne disease listeriosis. I was able to identify generalised transduction in L. monocytogenes which allowed the identification of the molecular basis for the abortive infection mutant phenotype of Listeria monocytogenes. This discovery has implications for vaccine development and the understanding of the physiological basis of bacterial pathogenesis Molecular and cellular computing and synthetic biology. I have had long term collaborations with computer scientists to use DNA as a computing matrix (molecular computing) and to construct Boolean Nand gate logic circuits in gene expression pathways to carry out computation tasks (cellular computing). We also investigated the use of innate pattern formation properties of bacteria to carry out computations.