Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
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.
How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head ....How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head development, and to characterise the function of selected components of this network to refine its architecture and define the dynamics of the network. The knowledge may improve our understanding of the molecular mechanism underpinning the naturally-occurring variation in the forms of major body parts, and of how genes and signals work cooperatively to build an embryo.Read moreRead less