Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene exp ....Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene expression data supports homology between sponge and eumetazoan tissues and body plans. This project could illuminate the evolutionary history of the animal body plan.Read moreRead less
Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across f ....Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across fly species and vertebrates, and their functional effect on testis morphogenesis and distortion of female/male sex-ratio. The project also studies splicing-dependent small RNAs and miRNA-target interaction. This research could have applications from animal development to human pathology.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This p ....Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This project aims to determine the basis of ion permeation and selectivity in the channels and explain the mechanisms of action for a number of common drugs. This will provide a foundation for future drug development to target specific channels for improved treatment of epilepsy, chronic pain and arrythmias. Read moreRead less
The identification of Mycosphaerella graminicola effectors that promote pathogenicity on wheat. Fungal diseases are one of the greatest challenges to sustainable wheat production in the 21st century. Septoria tritici blotch is one such disease as it inflicts millions of tonnes in yield losses per annum. This project will identify the molecular basis of Septoria tritici blotch and assess its potential as an Australian biosecurity threat.
The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter protein ....The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter proteins. The knowledge gained might help to combat Apicomplexan parasites by targeting these transporters’ native functions.Read moreRead less
Mimetics and small chemical compounds for hemopoietic stem cell mobilisation. This project will result in the design and synthesis of new chemical compounds that could be used clinically to help collect blood stem cells for bone marrow transplantation. For patients this will mean more effective and less painful ways to collect stem cells and better transplant outcomes. There is a large, ongoing international market for this type of drug and likelihood of significant financial benefit.
REdefining metabolic Schemes and Pathways In plant leaf REspiration. Leaf respiration-related metabolism in terrestrial vegetation liberates considerable amounts of carbon dioxide, ammonia and hydrogen sulphide into the atmosphere. Such gaseous losses are detrimental to biomass production but respiration also sustains nutrient assimilation and biosyntheses. This project aims to describe flux patterns in respiratory metabolism and disentangle interactions with other pathways such as photorespirat ....REdefining metabolic Schemes and Pathways In plant leaf REspiration. Leaf respiration-related metabolism in terrestrial vegetation liberates considerable amounts of carbon dioxide, ammonia and hydrogen sulphide into the atmosphere. Such gaseous losses are detrimental to biomass production but respiration also sustains nutrient assimilation and biosyntheses. This project aims to describe flux patterns in respiratory metabolism and disentangle interactions with other pathways such as photorespiration and nitrogen assimilation. It will exploit stable isotopes to quantify metabolic partitioning and show coordination between major processes. It will establish key mechanisms by which respiration dictates plant carbon balance and contributes to identifying metabolic bottle-necks in plant primary production.Read moreRead less
The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity f ....The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity for pharmaceutics and agriculture, and understand their biological roles in pathogens. Expected outcomes include sources of bioactive molecules and better management of fungal diseases in crops and humans.Read moreRead less
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less