Discovery of new metabolic functions in Plasmodium parasites. This research will provide new understanding about the metabolism of parasites, such as those that cause malaria. These parasites have evolved bespoke metabolic networks to survive in diverse host environments including mosquitos and humans. Previous studies have revealed many unique genes and metabolites in these organisms, but their biochemical function is not known. This project will use state-of-the-art metabolomics and proteomics ....Discovery of new metabolic functions in Plasmodium parasites. This research will provide new understanding about the metabolism of parasites, such as those that cause malaria. These parasites have evolved bespoke metabolic networks to survive in diverse host environments including mosquitos and humans. Previous studies have revealed many unique genes and metabolites in these organisms, but their biochemical function is not known. This project will use state-of-the-art metabolomics and proteomics technology to accurately identify novel metabolites produced by the parasites, and discover the enzymes that are responsible for their synthesis. This work will not only advance our understanding of cellular metabolism, but will provide new opportunities for future biotechnology applications.Read moreRead less
Characterisation of a powerful molecular motor, the FtsK DNA translocase. The FtsK protein is a fast and powerful molecular motor, a pump that can, and does, move an entire bacterial chromosome. This project will uncover the detail of the mechanism used by this motor to convert the cell's chemical energy source Adenosine Triphosphate (ATP) into movement of DNA; revealing the molecular detail of a fast and powerful motor.
Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Austra ....Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Australia the incidence of cancer is predicted to rise dramatically - improved treatment outcomes and better use of chemotherapeutics will be of obvious national benefit. The development of new tumour-targeted agents is the subject of joint Intellectual Property between Australia and the USA, offering potential economic benefit. Read moreRead less
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
How cells control autophagy during nutrient starvation and stress. This project aims to understand how human cells form autophagosomes during nutrient starvation and stress conditions, including bacterial invasion and mitochondrial dysfunction. Autophagy is a conserved intracellular degradation pathway which fungi, plants, insects and mammals use to respond to starvation and stress. Autophagy can provide nutrients by recycling cellular components, and protect cells from dysfunctional organelles ....How cells control autophagy during nutrient starvation and stress. This project aims to understand how human cells form autophagosomes during nutrient starvation and stress conditions, including bacterial invasion and mitochondrial dysfunction. Autophagy is a conserved intracellular degradation pathway which fungi, plants, insects and mammals use to respond to starvation and stress. Autophagy can provide nutrients by recycling cellular components, and protect cells from dysfunctional organelles and invading pathogens by mediating their removal. The autophagosome is a vesicular membrane structure important in autophagy by delivering material destined for degradation to the lysosome. Better understanding how plant and human cells protect themselves during starvation and stress is expected to benefit the environment and economy.Read moreRead less
Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australi ....Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australian population. The training of post-graduate students is an integral component of this study and thus will contribute to building national research capacity. International collaborations and new discoveries will also contribute to the recognition of Australian research.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Defining the cellular impacts of protein aggregation in neurodegenerative disease with an aggreomics platform. The brain disease Huntington’s is caused by abnormally shaped proteins that assemble into toxic clusters. This project will design new bioprobes to track how these clusters form and cause damage to cells. This strategy will also provide new opportunities for discovering novel therapeutic targets.
DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. Read moreRead less
Roles of the kynurenine pathway in physiological and pathological brain function. This project will aim to study the metabolism of the essential amino acid tryptophan in the brain and its involvement in diseases including multiple sclerosis and brain tumours.