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
Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The kn ....Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The knowledge gained from this work will inform and guide future novel approaches, such as in assisted reproductive technologies or regenerative medicine.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
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.Read moreRead less
Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Disse ....Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Dissecting how exosomes are produced at the fundamental level will provide significant benefits such as a deeper understanding of how cells maintain normal cellular functions.Read moreRead less
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
The structural biology of trace metal trafficking across membranes. This project aims to investigate how essential trace element nutrients are recognised and specifically acquired and expelled by bacterial cells. Cells are surrounded by biomembranes that separate and protect them from their environments. Embedded within these membranes are proteins that perform essential functions. In bacteria, membrane proteins are responsible for the uptake and elimination of trace elements that are required f ....The structural biology of trace metal trafficking across membranes. This project aims to investigate how essential trace element nutrients are recognised and specifically acquired and expelled by bacterial cells. Cells are surrounded by biomembranes that separate and protect them from their environments. Embedded within these membranes are proteins that perform essential functions. In bacteria, membrane proteins are responsible for the uptake and elimination of trace elements that are required for survival. This project will investigate the features of integral membrane proteins that allow discrimination between cargo, by defining their three dimensional architectures using X-ray crystallography. This will contribute to the field of membrane protein structural biology and fundamental discoveries in the area of cellular trace element homeostasis and toxicity.Read moreRead less
Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate n ....Understanding the determinants of age-related muscle wasting in females . This project aims to investigate the fundamental mechanisms underlying age-related muscle wasting in females. Females live longer than males and are more susceptible to the consequences of muscle ageing. Yet, our current knowledge is overwhelmingly inferred from findings from male cohorts. By comprehensively mapping the functional, molecular and epigenetic mechanisms of ageing in female muscle, this project will generate new, fundamental knowledge that will allow a unique interpretation of previous research through a sex-specific lens. This knowledge will contribute to better inform sex-specific models of research and practice in the future, ultimately delivering economic and social benefits for Australia and international communities.Read moreRead less
How does glycosylation shape protein function within Burkholderia? Protein glycosylation, the chemical addition of sugars to proteins, is an important but poorly understood aspect of bacterial physiology. This project aims to build on our recent discovery of the conservation of O-linked glycosylation across the Burkholderia genus to understand the function of this modification. Using cutting-edge proteomics, novel expression systems and molecular approaches this project will reveal the role of g ....How does glycosylation shape protein function within Burkholderia? Protein glycosylation, the chemical addition of sugars to proteins, is an important but poorly understood aspect of bacterial physiology. This project aims to build on our recent discovery of the conservation of O-linked glycosylation across the Burkholderia genus to understand the function of this modification. Using cutting-edge proteomics, novel expression systems and molecular approaches this project will reveal the role of glycosylation in Burkholderia species. This innovative project will provide a comprehensive understanding of how glycosylation contributes to Burkholderia protein function and how these systems can be harnessed for the creation of bespoke glycoconjugatesRead moreRead less
Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research ....Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research is important because DNA damage threatens organism survival and this project has the potential to define how this genomic threat is resolved at the single molecule level. The benefit of this research is a fundamental insight into DNA repair biology and development of imaging technology to quantify genome function.Read moreRead less