How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
New targets for antiviral therapies. The ability of dangerous viruses to cause lethal disease depends on their capacity to evade the immune system of infected hosts. This project will uncover at the molecular level the strategies used by viruses to disable immune responses; this will identify new ways to treat incurable diseases, by disabling the virus' defences against the immune system.
The combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.
Control of cell fate decisions in neurogenesis: use of embryonic stem cells to investigate key signalling systems and gene expression programs. Human embryonic stem cells (hESC) have the potential to provide an unlimited source of specific subtypes of human neurons for basic studies in neuroscience and biomedical applications. The use of hESC is limited at present by a lack of control over lineage commitment during differentiation in vitro. This project will use engineered reporter hESC lines t ....Control of cell fate decisions in neurogenesis: use of embryonic stem cells to investigate key signalling systems and gene expression programs. Human embryonic stem cells (hESC) have the potential to provide an unlimited source of specific subtypes of human neurons for basic studies in neuroscience and biomedical applications. The use of hESC is limited at present by a lack of control over lineage commitment during differentiation in vitro. This project will use engineered reporter hESC lines to investigate which cell signalling pathways and gene expression programs are involved in controlling cell fate. The project will result in improved protocols for hESC differentiation allowing enrichment of cultures with specific neuronal subtypes, and significant advances in the understanding of neuronal lineage commitment and maturation during brain development. Read moreRead less
How protein tyrosine phosphatases select their substrates. Protein tyrosine phosphatases (PTPs) are enzymes that control the response of cells to divergent environmental stimuli. This project will determine how individual PTPs exert selective effects on cellular communication networks to coordinate organismal development, growth and survival.
Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for i ....Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for integrating nuclear actions that has the potential to create a signal transduction circuit triggered by environmental or genetic factors. This information is crucial in defining the molecular logic of signalling events that may be ultimately targeted to control cell growth, differentiation and survival.Read moreRead less
Uncovering New Mechanisms of Metabolite-Sensing and Signaling. This project aims to understand how cells sense changes in metabolic activity, to ensure energy demands are matched with nutrient supply. Our proposal will fill critical gaps in our understanding of the molecular mechanisms underlying metabolic sensing. This will generate new knowledge with far reaching potential for Australian industries that rely on the propagation and utilization of living organisms, including agriculture, biotech ....Uncovering New Mechanisms of Metabolite-Sensing and Signaling. This project aims to understand how cells sense changes in metabolic activity, to ensure energy demands are matched with nutrient supply. Our proposal will fill critical gaps in our understanding of the molecular mechanisms underlying metabolic sensing. This will generate new knowledge with far reaching potential for Australian industries that rely on the propagation and utilization of living organisms, including agriculture, biotechnology and brewing, as well as knowledge relevant to sporting performance and the metabolic dimensions of ageing. This project will support advanced training of early career researchers and PhD students, which will expand Australian research capabilities and contribute to a producing a highly skilled workforce.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput pro ....The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput protein analysis. The anticipated outcomes will be to define the molecular steps that govern the membrane-bound machinery on endosomes that directs endosomal maturation. This should provide significant benefits in delineating a process that is linked to almost all aspects of cell life.Read moreRead less