Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quali ....Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quality of life for older Australians and address the physical realities of an ageing workforce. Benefits extend to enhancing workplace safety and productivity, improving farming efficiencies for livestock and aquaculture industries, and training emerging leaders in the biological sciences.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the ....How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the activation of this system to trigger the local generation of AngII. This project addresses the question of where exactly in the heart the RAS components are turned on, how they interact to generate AngII and whether the activation of the local RAS is beneficial or not to cardiac function. The findings should provide critical insights into an important hormonal system.Read moreRead less
From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a nov ....From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a novel and unique way. This combination is in itself a major advancement of scientific methods that will accelerate discovery in the field of systems biology. In this respect, the project is a premier example of the priority goal Breakthrough Science and of the national research priority Frontier Technologies.Read moreRead less
Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of ....Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of productivity, and paralleled decline in the resident macrophages in these organs may be a common ageing mechanism. Demonstration that altered macrophage biology unpins decline in blood and bone may prolong peak health and increase productivity in the ageing population.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347607
Funder
Australian Research Council
Funding Amount
$306,000.00
Summary
FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged ex ....FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged expertise as well as priority within their respective institutions. In addition, it will facilitate wide-ranging collaborative arrangements to further develop and exploit this research area.Read moreRead less
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundament ....Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundamental insights into how SIK3 in the hypothalamic neurons regulates energy homeostasis. Benefits include improving population health and wellbeing, informing the development of new bio-medical technologies, and expanding the capabilities of Australia’s next generation of researchers.
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Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five deca ....Improving clostridial toxoid production through molecular fermentation maps. This project aims to improve vaccine production by generating detailed molecular maps of fermentation which will be used to design superior fermentation processes with reduced cost. Toxoid vaccines, used routinely in the livestock industry to prevent animal-disease caused by pathogenic Clostridia, are produced using batch fermentation processes. These processes have undergone limited optimisation over the past five decades. Low titres and frequent batch failures greatly affect capital use and represent a significant cost. In addition, current optimisation approaches are limited by the use of expensive and noisy endpoint assays. This project aims to use high-throughput chemistry (multi-omics) that overcome these limitations.Read moreRead less