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
Transcription factor nuclear residency as a driver of gene expression. Persistently active proteins can stay in the nucleus to drive cell growth and prevent cell death. This project will define how one specific active protein can remain in the nucleus and regulate gene expression through the action of unique ribonucleic acid (RNA) molecules. The results will enable persistent gene activation to be manipulated in cancer.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms ....Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms of function remain poorly characterised and seldom considered. The expected outcome of better understanding mechanisms through which microRNAs work should provide significant benefit to safe and effective development of microRNAs for future agricultural or therapeutic application.Read moreRead less
Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcripti ....Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcription on a genome-wide scale and will thereby reveal the full extent of mechanisms by which these important genetic switches control gene expression networks the characteristics of cells. This is of fundamental significance to our understanding of gene regulation.Read moreRead less
Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of ....Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of way in which respiratory gene expression is controlled in bacterial species for which Escherichia coli is not a suitable model. 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.
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth contr ....The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth control, cell fate specification, cellular signalling and eye vision. These discoveries are likely to enhance international collaborations and stimulate new research.Read moreRead less
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.