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
New methods for structure analysis of proteins and protein interactions. This project will advance nuclear magnetic resonance (NMR) technologies pioneered at the Australian National University which employ site-specific attachment of paramagnetic metal tags to proteins. A new and diverse set of strategies will dramatically extend the range of applications to targets of interest in the fight against cancer and bacterial infections.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
Ion transport in the malaria parasite and parasitised erythrocyte. This work will contribute to the national research effort in parasitology (an area in which the ARC has established a Research Network), as well as laying the groundwork for subsequent efforts (not part of this grant) to develop new antimalarial strategies. Although not yet endemic in Australia, malaria is a serious problem in the local region and, as the major developed nation in the region Australia has an obligation to make ....Ion transport in the malaria parasite and parasitised erythrocyte. This work will contribute to the national research effort in parasitology (an area in which the ARC has established a Research Network), as well as laying the groundwork for subsequent efforts (not part of this grant) to develop new antimalarial strategies. Although not yet endemic in Australia, malaria is a serious problem in the local region and, as the major developed nation in the region Australia has an obligation to make a significant contribution to research in this area. The work proposed here will contribute to Australia's meeting this obligation.Read moreRead less
Amino acid transporters and the chloroquine resistance transporter of the intracellular malaria parasite. This work entails an ongoing collaboration between three independent research groups with highly complementary expertise and experience. It will make a significant contribution to the maintenance of Australia's scientific capabilities and training opportunities. The project will yield important insights into the biology of the causative agent of a major human disease, and the mechanism by ....Amino acid transporters and the chloroquine resistance transporter of the intracellular malaria parasite. This work entails an ongoing collaboration between three independent research groups with highly complementary expertise and experience. It will make a significant contribution to the maintenance of Australia's scientific capabilities and training opportunities. The project will yield important insights into the biology of the causative agent of a major human disease, and the mechanism by which the malaria parasite has developed resistance to antimalarial drugs. Although not yet endemic in Australia, malaria is a serious problem in the local region and this work will help Australia meet its obligations to carry out high-quality research that advances our knowledge in this area.
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Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from ....Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from sexually compatible species and short effective time spans in the field. Building on previous research, this project aims to characterise the molecular basis of the Toll/interleukin-1 receptor domain-mediated nicotinamide adenine dinucleotide (NAD+) cleavage and the structural architecture of plant NLR complexes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Understanding the molecular function of plant disease resistance proteins, pathogen effectors and their interaction to protect Australian agriculture. This project aims to understand the processes that enable resistant plants to detect and respond to pathogen attack. The acquired knowledge will form the foundation for durable plant disease resistance measures that can be applied to a wide range of crop diseases in an environmentally sustainable manner.
Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these dat ....Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these data, the project aims to characterize the structures of the signaling molecules resulting from TIR (Toll/interleukin-1 receptor) domain-mediated NAD+ cleavage and the structural architecture of plant NLR resistosomes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101035
Funder
Australian Research Council
Funding Amount
$369,500.00
Summary
Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not under ....Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not understood. Recent work has identified a unique Apicomplexan sodium transporter and revealed a number of chloride transporter candidates. Using a combination of molecular biology and physiological techniques, this project aims to characterise the Apicomplexan sodium transporter in detail and elucidate the molecular mechanisms of chloride transport.Read moreRead less