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.
Understanding the molecular basis of fungal rust diseases in plants. This project aims to utilise structural biology, biochemistry and molecular biology approaches to substantially deepen our understanding of rust fungi-plant interactions. Fungal rust pathogens cause disease and significant yield losses in our most important food crops. During colonisation, rust fungi utilise secreted effector proteins to cause plant disease. Effectors can also be recognised by plant immunity receptors, leading ....Understanding the molecular basis of fungal rust diseases in plants. This project aims to utilise structural biology, biochemistry and molecular biology approaches to substantially deepen our understanding of rust fungi-plant interactions. Fungal rust pathogens cause disease and significant yield losses in our most important food crops. During colonisation, rust fungi utilise secreted effector proteins to cause plant disease. Effectors can also be recognised by plant immunity receptors, leading to resistance. The intended outcome of this work is to generate knowledge that can be used for the development of disease management and engineering strategies to protect plants from rust fungi. This should provide significant benefits to agricultural productivity and global food security.Read moreRead less
Unlocking secrets of fertility restoration for hybrid breeding in crops. Hybrid varieties give higher and more stable yields than conventional lines, but a cost-effective system to make hybrid seed on a commercial scale is still missing for economically important crops like wheat or barley. By elucidating the mode of action of a new type of restorer gene plus exploiting ancient or exotic wheat and barley collections this project will reveal aspects of largely understudied mechanisms underlying f ....Unlocking secrets of fertility restoration for hybrid breeding in crops. Hybrid varieties give higher and more stable yields than conventional lines, but a cost-effective system to make hybrid seed on a commercial scale is still missing for economically important crops like wheat or barley. By elucidating the mode of action of a new type of restorer gene plus exploiting ancient or exotic wheat and barley collections this project will reveal aspects of largely understudied mechanisms underlying fertility restoration in wheat and barley. The expected outcomes of the proposed research have the potential to deliver new tools for hybrid seed production programs in wheat and barley. Higher and more stable yields from hybrids will ensure food security in the face of an uncertain climate and growing human population.Read moreRead less
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.
Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform o ....Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform of immediate use in the agriculture sector and for animal model alternatives. The benefit will be widespread, ensuring the growth and sustainability of our health and agriculture sector. The project will increase public understanding of protein delivery technologies, aiding in technology adoption.Read moreRead less
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