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
Plant immunity to fungal and bacterial pathogens. Since 2003, the Australian wheat crop has been threatened by a continuing stripe rust epidemic, which has required an additional production expense of at least $100 million per annum in fungicides. This Australian National University (ANU) - Commonwealth Scientific and Industrial Research Organisation (CSIRO) joint proposal aims to exploit the next-generation genome sequencing and associated bioinformatic and proteomic methods which are poised to ....Plant immunity to fungal and bacterial pathogens. Since 2003, the Australian wheat crop has been threatened by a continuing stripe rust epidemic, which has required an additional production expense of at least $100 million per annum in fungicides. This Australian National University (ANU) - Commonwealth Scientific and Industrial Research Organisation (CSIRO) joint proposal aims to exploit the next-generation genome sequencing and associated bioinformatic and proteomic methods which are poised to revolutionise biology to investigate the wheat-fungus interaction. We will develop new effective approaches for environmentally benign stripe rust control based on new knowledge about how this fungus causes disease and avoids the wheat's immune surveillance system.Read moreRead less
Phenotypic plasticity in plants: evolution, adaptation and its relevance in a changing climate. Plants are highly responsive to the conditions under which they grow, but the combination of conditions they experience will be altered by climate change. This research into plant responses to novel environments posed by climate change will assess whether we can breed for more responsive crops or predict native plant tolerance of climate change.
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
Linking Stress Tolerance to Molecular Evolution of Grass Stomata. Salinity and drought are two detrimental environmental stresses, affecting agricultural productivity and ecosystem health in Australia and around the world. This project will focus on the evolutionary, physiological and molecular aspects of stomatal regulation between wheat, barley and their wild relatives for salinity and drought tolerance. This project will advance the scientific knowledge in the evolution of stomatal regulation ....Linking Stress Tolerance to Molecular Evolution of Grass Stomata. Salinity and drought are two detrimental environmental stresses, affecting agricultural productivity and ecosystem health in Australia and around the world. This project will focus on the evolutionary, physiological and molecular aspects of stomatal regulation between wheat, barley and their wild relatives for salinity and drought tolerance. This project will advance the scientific knowledge in the evolution of stomatal regulation in two staple crops wheat and barley. The project will also assist plant breeders with increasing crop salinity and drought tolerance for global food security.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
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
Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit ....Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit it for our own benefit is needed. This project aims to anticipate evolution by simulating it in the laboratory, allowing for the best preparation for change. New pesticides will be designed to combat insecticide resistance based upon the molecular structure of an insect CBE. This project aims to exploit these newly evolved enzymes to create biosensors and decontamination agents.Read moreRead less
Deciphering how plants control water and salt co-transport. This project aims to increase our understanding of how plant cells regulate solute transport. Crop growth depends on water uptake and transport, and the rapid movement of water across plant cell membranes requires transporters such as aquaporins. Preliminary data indicates that a series of signals can switch aquaporins between functioning as highly selective water channels and salt transport channels. The project aims to reveal the mole ....Deciphering how plants control water and salt co-transport. This project aims to increase our understanding of how plant cells regulate solute transport. Crop growth depends on water uptake and transport, and the rapid movement of water across plant cell membranes requires transporters such as aquaporins. Preliminary data indicates that a series of signals can switch aquaporins between functioning as highly selective water channels and salt transport channels. The project aims to reveal the molecular pathways that regulate water and salt co-transport, using genetics, molecular biology, and electrophysiology data to decipher how plants regulate and coordinate aquaporin solute transport during growth and in osmotic adjustment. The project has the potential to lead to improvements in crop-plant solute transport traits, enhanced agricultural productivity, and yield stability in saline and water limited environments.Read moreRead less