How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pat ....How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pathways required for enucleation. The project will provide a molecular and cellular road map of enucleation that may be utilised to enhance the bulk therapeutic in vitro production of red blood cells for veterinary and human purposes.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
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
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This ....The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This project is expected to increase understanding of nucleotide sugar transport and develop and enhance the biological toolbox for applications involving modelling and engineering of plants, synthesis of industrial biopolymers and production of functional foods.Read moreRead less
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
Molecular-genetic organization and evolution of dinoflagellate mitochondria. Dinoflagellates are unicellular organisms that are important parts of the biota as significant primary producers of the oceans. Certain dinoflagellates form essential symbionts of reef-forming corals and loss of the symbiont causes coral bleaching and death, a phenomenon linked to global warming. Dinoflagellate blooms are also notorious for causing fish kills and human illnesses such as paralytic shellfish poisoning. My ....Molecular-genetic organization and evolution of dinoflagellate mitochondria. Dinoflagellates are unicellular organisms that are important parts of the biota as significant primary producers of the oceans. Certain dinoflagellates form essential symbionts of reef-forming corals and loss of the symbiont causes coral bleaching and death, a phenomenon linked to global warming. Dinoflagellate blooms are also notorious for causing fish kills and human illnesses such as paralytic shellfish poisoning. My studies of the mitochondrion will address a major aspect of the biology of this poorly understood group. Mitochondrial function is often a target for drugs and other controlling agents, and therefore these studies could offer scope to better interpret and manage dinoflagellates in our environment.Read moreRead less
Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing feat ....Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing features of the Project will be the international, integrative, and multidisciplinary approach towards addressing this major challenge in plant biology and the potential of the fundamental scientific discoveries to benefit end-users in the food, feed and beverage industries.Read moreRead less