Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
New genomic technologies are revolutionizing biological research. RNA-seq is a recently developed high-throughput sequencing technology that provides scientists with much more detail how genes are regulated and expressed than any earlier technology. New tools developed by Professor Gordon Smyth are allowing researchers to use RNA-Seq technology to more accurately determine which genes are genuinely changing in the development of cancers and in response to cancer treatments.
Discovery Early Career Researcher Award - Grant ID: DE120102575
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Exploring new territory in climatic adaptation research: integrating molecular genetics with species' thermal tolerance limits. Predicting species' responses to environmental change requires mechanistic links between whole-organism physiological stress responses and underlying cellular mechanics. This project integrates cutting-edge methods in molecular and evolutionary genetics to probe species' responses to environmental change in the context of a warming environment.
Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importan ....Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importance on the regulatory function of miRNAs. Such information is critical in the future development of targeted therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100652
Funder
Australian Research Council
Funding Amount
$345,000.00
Summary
Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is h ....Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is how the balance between self-renewal and differentiation is regulated in these cells, nor how the control of this fate decision impacts on optimal organ development. This project aims to dissect the molecular identity, regulation, and influence of this stem cell population on kidney development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100085
Funder
Australian Research Council
Funding Amount
$414,864.00
Summary
Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is ach ....Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is achieved by examining the molecular pathways that are activated following genetic mutation. This project is expected to strengthen Australian reputation in evolutionary genetics, and in turn enhance our understanding of how organisms adapt to changing environments.Read moreRead less
Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE120100434
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Estrogen-mediated regulation of gene expression via transcriptional and translational control: complementary, synergistic or opposing responses? Hormones dictate cellular behaviour by activating pre-programmed responses. The sex hormone estrogen affects cell fate by regulating the gene expression, but it is unknown to which extent this response occurs via activation of genes or control of already transcribed gene. The project will investigate how the cell integrates the complex estrogen signals.