Infectious diseases are one of the leading causes of death and morbidity worldwide. In the last two decades the incidence of diseases caused by bacteria has increased dramatically with old pathogens re-emerging, often in a more virulent form, and new infectious agents appearing. Many pathogenic microbes are becoming increasingly resistant to antibiotics so that the need for new therapeutic targets is urgent. We will develop new antimicrobial chemotherapies by targeting DsbA, a specific factor in ....Infectious diseases are one of the leading causes of death and morbidity worldwide. In the last two decades the incidence of diseases caused by bacteria has increased dramatically with old pathogens re-emerging, often in a more virulent form, and new infectious agents appearing. Many pathogenic microbes are becoming increasingly resistant to antibiotics so that the need for new therapeutic targets is urgent. We will develop new antimicrobial chemotherapies by targeting DsbA, a specific factor involved in the generation of bacterial virulence. This protein is found in most bacteria and contributes to pathogenicity by promoting the formation of toxins and virulence factors. We will design specific inhibitors of DsbA by using a structure-based approach, implementing the leading edge technologies of fragment-based lead discovery by crystallography and NMR. We will then optimise the fragments to develop lead compounds and evaluate their suitability as DsbA inhibitors by in vitro and in vivo assays.Read moreRead less
Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such tr ....Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such training is essential for developing a future pool of skilled Australian scientists to staff and utilise the major national infrastructure developments represented by the Replacement Research Reactor and Australian Synchrotron, as outlined in the National Research Priority "Frontier Technologies".Read moreRead less
Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Aus ....Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Australian Synchrotron and the OPAL Research Reactor.Read moreRead less
Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of ....Structure and temperature adaptation of chaperonin TF55 from Sulfolobus solfataricus. Our work has future potential both for biotechnology and for medical therapies. The cages formed by chaperonin subunits and their ability to bind to specific targets could lead to their application as nano-vesicles, could facilitate expression of eukaryotic proteins in bacteria and could help to prevent or dissolve protein aggregates. With Australia's ageing population, we can expect an increasing prevalence of pathologies such as Alzheimer's and Parkinson's disease and other diseases that arise from protein mis-folding and aggregation, including myopathies and cataracts. A participation of chaperonins has been implicated in these age-related diseases and demands detailed structural and functional investigations.Read moreRead less
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.Read moreRead less
Molecular toxinology of Australia's lesser known venomous snakes. This proposal represents a tremendous opportunity for biodiscovery from venomous snakes. This will be achieved through the researchers' unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate stude ....Molecular toxinology of Australia's lesser known venomous snakes. This proposal represents a tremendous opportunity for biodiscovery from venomous snakes. This will be achieved through the researchers' unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237427
Funder
Australian Research Council
Funding Amount
$269,000.00
Summary
Equipment for Fluorescence-Based Cellular Analysis. The requested equipment is needed by a large grouping of highly productive researchers to carry out work across a very broad range of fields that is otherwise difficult or impossible to perform. The new equipment will facilitate obtaining many exciting and important outcomes, including identification of: (i) mechanisms controlling cell death, (ii) natural biological products that may have commercial applications (eg anti-fouling agents), (iii) ....Equipment for Fluorescence-Based Cellular Analysis. The requested equipment is needed by a large grouping of highly productive researchers to carry out work across a very broad range of fields that is otherwise difficult or impossible to perform. The new equipment will facilitate obtaining many exciting and important outcomes, including identification of: (i) mechanisms controlling cell death, (ii) natural biological products that may have commercial applications (eg anti-fouling agents), (iii) "probiotic" bacteria and vaccines that may be used to protect animals from disease, and (iv) mechanisms by which changes in human lens proteins contribute to the development of cataract.Read moreRead less
The chemical, biochemical, genetic and ecological basis of pollinator-driven speciation in Australian sexually deceptive orchids. The Australian biota offers unique opportunities for illuminating ecological and evolutionary processes of worldwide importance. Focussing on Australian sexually deceptive orchids, this study offers a model system for studies of plant speciation that has already captured the interest of the public, educators and scientists around the world. The project will produce mu ....The chemical, biochemical, genetic and ecological basis of pollinator-driven speciation in Australian sexually deceptive orchids. The Australian biota offers unique opportunities for illuminating ecological and evolutionary processes of worldwide importance. Focussing on Australian sexually deceptive orchids, this study offers a model system for studies of plant speciation that has already captured the interest of the public, educators and scientists around the world. The project will produce multiple graduate students with high quality, cross-disciplinary training. Expertise and tools developed will contribute directly to the conservation of endangered Australian orchids. Thus the knowledge obtained from this research will have immediate practical benefits for the sustainable use of Australia's biodiversity.Read moreRead less