Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other pote ....Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other potentially valuable compounds. In addition to providing unprecedented insight into the ecology and biosynthesis of this enigmatic toxin, the data generated will enable improved management of seafood safety and provide a foundation for the future development of novel neuroactive compounds.Read moreRead less
Role of ferroxidases in intestinal iron transport. This project will investigate the mechanism by which the body absorbs the essential nutrient iron from the diet. These studies will enhance our knowledge of an important nutritional pathway and improve our capacity to treat diseases where iron absorption is defective, such as the iron loading disorder haemochromatosis.
Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids. This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform fo ....Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids. This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform for generating new molecules with desirable biological activities that can be readily scaled up for sustainable bioproduction. This will provide significant benefits to Australia through the development of cutting-edge biotechnologies as well as the discovery of new pharmaceuticals, veterinary products and agrichemicals.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less