Discovery of invertebrate attractants and toxins from diverse Actinomycetes
This PhD project will be based at the University of Toronto with a 24 month stay at the University of Melbourne.
Actinomycete bacteria are prolific producers of an astounding array of small molecules, known as specialized metabolites. These chemicals feature prominently in clinical medicine as antibiotics, antifungals, immunosuppressants and anticancer agents, and many also have effects on other organisms, including as insect attractants or toxins.
Interestingly, there are several examples of actinomycetes forming mutually beneficial associations with invertebrates. For example, leaf-cutter ants cultivate antibiotic-producing actinomycetes that in turn produce a range of antibiotics to protect the ants’ fungal food source from infection or from being out-competed by other microbes. Likewise, Philanthus wasps coat their larvae in antibiotic-producing Streptomyces bacteria to protect them from infection with other microbes. However, many examples also exist of actinomycete-derived molecules that are specifically toxic to invertebrates. The best known example is avermectin produced by the actinomycete Streptomyces avermitilis, which is highly toxic against parasitic worm species and has been used in the developing world to almost eradicate human onchocerciasis (river blindness). While some work has been performed on a range of Streptomyces species and their interaction with insects, the story is far from complete and further opportunities exist, especially among less-well studied actinomycetes to identify invertebrate attractants and toxins.
This project will use a several insect model systems to investigate attractant and repellant (or toxic) phenotypes of ~1000 individual actinomycete isolates. Individual actinomycetes producing the desired phenotype will be selected and the responsible compounds will be isolated and have their structures fully elucidated. At the same time, the selected isolates will have their genomes sequenced to inform the development of mutant strains that will connect genes to molecules. We anticipate this project will provide a range of previously unseen invertebrate-active compounds, potentially providing a pathway for their further development and use in the clinic.
Prof Justin Nodwell (University of Toronto)
Dr Sacha Pidot (University of Melbourne)
How to Apply