Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.
Using ‘omic and digital technologies toward better fasciolosis control. In Australia, liver fluke disease caused by Fasciola hepatica causes major economic losses to livestock production. Triclabendazole is the most effective drug for parasite control, however, resistance to this drug has emerged and continues to spread in Australia. This project expects to create a novel resource to identify new drug targets, generate new knowledge about the genetic composition of F. hepatica populations and un ....Using ‘omic and digital technologies toward better fasciolosis control. In Australia, liver fluke disease caused by Fasciola hepatica causes major economic losses to livestock production. Triclabendazole is the most effective drug for parasite control, however, resistance to this drug has emerged and continues to spread in Australia. This project expects to create a novel resource to identify new drug targets, generate new knowledge about the genetic composition of F. hepatica populations and unravel the genetic determinants underlying triclabendazole resistance. The curation of functionally-annotated genetic data for F. hepatica populations will underpin the development of diagnostic tests, drugs and vaccines to deliver a new generation of intervention strategies to control liver fluke disease.Read moreRead less
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
How the immune system recognises vitamin B-based allergies. This project aims to evaluate the range of molecules that can stimulate vitamin B-reactive T cells in mammals and amphibians, and the degree of conservation or variation in these molecules among diverse microorganisms. T cells are immune cells that recognise foreign molecules, including peptides, lipids and vitamin B metabolites, bound to specialised antigen-presenting molecules. In mammals, Mucosal Associated Invariant T cells, still p ....How the immune system recognises vitamin B-based allergies. This project aims to evaluate the range of molecules that can stimulate vitamin B-reactive T cells in mammals and amphibians, and the degree of conservation or variation in these molecules among diverse microorganisms. T cells are immune cells that recognise foreign molecules, including peptides, lipids and vitamin B metabolites, bound to specialised antigen-presenting molecules. In mammals, Mucosal Associated Invariant T cells, still poorly understood, recognise Vitamin B-based molecules. Combining immunology with structural biology and chemistry, this project aims to understand how the immune system detects molecules produced by diverse microorganisms.Read moreRead less
Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect ....Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect the cellular conversations that underpin immune protection. Revealing the mechanisms of cellular interactions during an immune response will have a major impact on development of targeted vaccines, and therapeutics (particularly for chronic infections and cancer), which are major health burdens.Read moreRead less
Transcriptional control of neural stem cell differentiation during development and disease. Understanding the molecular mechanisms that control how neural stem cells differentiate is critical to provide potential therapeutic treatment for neurodegenerative diseases and for brain cancer. This project will aim to discover, using an animal model system, the genes and molecules regulating these key biological processes.
Understanding the neuronal mechanisms underlying inherited epilepsies. Epilepsy is a serious disease that impacts severely on individuals and the community as a whole. Conservative estimates suggest a financial cost of more than $2 billion per annum. Drug treatment for this disease is often not adequate. Recent advances have allowed scientists to determine mutation in human genes that cause epilepsy. New models of epilepsy based on this knowledge will allow us to better understand what causes e ....Understanding the neuronal mechanisms underlying inherited epilepsies. Epilepsy is a serious disease that impacts severely on individuals and the community as a whole. Conservative estimates suggest a financial cost of more than $2 billion per annum. Drug treatment for this disease is often not adequate. Recent advances have allowed scientists to determine mutation in human genes that cause epilepsy. New models of epilepsy based on this knowledge will allow us to better understand what causes epilepsy enabling us to devise new and potent therapeutic strategies to treat the disease.Read moreRead less
Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods ....Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods to simplify the analysis of multimodal path-clamping data (Patch-seq). Expected outcomes will facilitate research collaboration and the reproducibility of accurate experimental replicates of the human brain. This will provide significant benefits in the global race to understand human brain computation mechanisms.Read moreRead less
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.