Discovery Early Career Researcher Award - Grant ID: DE240100827
Funder
Australian Research Council
Funding Amount
$458,737.00
Summary
Delineating the developmental requirements for stem-like T cells. Stem-like CD8 T cells are critical for sustaining long-term systemic T cell activity. The signalling required for their development, however, remains elusive. Integrating multidisciplinary expertise, cutting-edge technology and highly innovative methods, this project aims to define the signalling cues provided by tissue microenvironment that control the development and maintenance of stem-like T cells, and thereby dictate systemic ....Delineating the developmental requirements for stem-like T cells. Stem-like CD8 T cells are critical for sustaining long-term systemic T cell activity. The signalling required for their development, however, remains elusive. Integrating multidisciplinary expertise, cutting-edge technology and highly innovative methods, this project aims to define the signalling cues provided by tissue microenvironment that control the development and maintenance of stem-like T cells, and thereby dictate systemic immunity. This project is expected to generate fundamental knowledge on basic immunology and T cell biology, which can benefit the academic, public health and biotechnology sectors by enhancing the international standing of Australian research on basic immunology and fostering new commercial opportunities. Read moreRead less
Molecular Diagnosis And Therapy Of Autoimmune Disease Using Translational And Reverse Translational Approaches
Funder
National Health and Medical Research Council
Funding Amount
$2,331,372.00
Summary
We plan to translate our recent discoveries on human gene variants and molecules produced by immune cells (follicular T cells) into effective therapies for autoimmune diseases. This will involve understanding the mechanisms by which the genes and molecules regulate immune tolerance, stratifying patients with autoimmune disease using newly identified biomarkers, trialling existing biologicals according to affected molecular pathway, and taking novel targets through to commercialisation.
Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the ....Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the proposed project will develop a novel efficient, safe and notably biodegradable self-adjuvanting delivery system that can be fully customised to match an antigen of choice. This foundational research should provide important advances for commercial immune stimulatory applications.Read moreRead less
Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epi ....Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epigenetics and structural biology. It is expected that this work will improve understanding of this fundamental biological defence. This will allow us to identify the potential means to enhance the capacity of glyoxalase-1 to the future benefit of biological ageing.Read moreRead less
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insig ....Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.Read moreRead less
Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natu ....Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natural and anthropogenic activities. The outcomes will provide a unifying ecological framework to predict variation in microbiomes across different scales, ecosystem types and disturbances, and will generate critical knowledge for the development of effective microbiome products, a rapidly growing industryRead moreRead less
EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cel ....EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cell survival. This project advances basic and applied biology. Its outcomes will be relevant to several research areas and industries, specifically to the propagation of cell cultures that nowadays contributes to the production of a myriad of biotechnical and pharmaceutical commodities.
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