How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractabi ....How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractability of the model organism Drosophila and its simple, yet conserved blood cell system, this project will yield new insights into the mechanisms that govern the animal blood cell population. This will benefit our fundamental understanding of how animals maximise their health throughout life.Read moreRead less
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.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
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.Read moreRead less
Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowle ....Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of developmental biology.
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Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform o ....Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform of immediate use in the agriculture sector and for animal model alternatives. The benefit will be widespread, ensuring the growth and sustainability of our health and agriculture sector. The project will increase public understanding of protein delivery technologies, aiding in technology adoption.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
Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normal ....Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normally controlled and how it can be manipulated industrially. This should provide significant benefits, impacting stem cell biology (improving stem cell production), tissue engineering (improving growth of artificial tissues), veterinary science and agriculture (improving productivity).Read moreRead less
Purinergic signalling in placentation and vascular adaptation in pregnancy. Our traditional understanding of purinergic signalling in the placenta is significantly outdated and incomplete. The placenta is critical for reproduction in all eutherian mammals, delivering critical nutrition and oxygen to the developing fetus. This project aims to define the role of purinergic signalling as a critical mechanism driving placentation and angiogenesis. This is the first study of its kind and will use sop ....Purinergic signalling in placentation and vascular adaptation in pregnancy. Our traditional understanding of purinergic signalling in the placenta is significantly outdated and incomplete. The placenta is critical for reproduction in all eutherian mammals, delivering critical nutrition and oxygen to the developing fetus. This project aims to define the role of purinergic signalling as a critical mechanism driving placentation and angiogenesis. This is the first study of its kind and will use sophisticated models to improve our fundamental understanding and ability to manipulate mammalian reproduction via the purinoreceptors. This proposal builds on my skills and expertise; improving our knowledge of the processes driving placental and vascular morphogenesis and offers important discoveries for reproductive science.Read moreRead less
Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specif ....Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specificity and develop state-of-the-art modelling technologies to improve knowledge of environmental influence on endothelial cell fate and function. This should provide a new framework to modulate the adaptive capacities of endothelial cells and can potentially enable more predictive and targeted drug efficacy and safety testing.Read moreRead less