Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate re ....Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate regeneration. Ultimately, this works aims to understand the metabolic requirements for regeneration. Expected outcomes include scholarly publications revealing fundamental principles of regeneration, new resources and pipelines for the research community as well as training for research students.Read moreRead less
I am a molecular biologist determining the function of extracellular matrix proteins critical for development, function and repair of important tissues such as arteries, lung, kidney, eye and bone.
The Role Of Heterochromatin In Regulating Cellular Proliferation And Development
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the ....Fundamental to the development of a multicellular organism is that for each cell type performing a specialised function, a different set of genes are turned on with the remainder being shut off. One of the most significant unanswered questions in biology is how a cell-type specific gene expression profile is established during early development. The answer to this question has important implications in understanding normal and abnormal cellular processes. Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein (histones) to form a structure known as chromatin. It has become clear that the chromatin structure encompassing a gene is the critical factor that determines whether a gene is expressed or silenced. We propose that developmental and cell-type specific mechanisms operate in a cell to assemble genes into highly specialised chromatin structures that permit (euchromatin) or restrict (heterochromatin) gene expression. In other words, the genome of each different cell type is organised into a unique and dynamic chromatin pattern and this pattern determines the gene expression profile. This investigation will show that the critical cellular mechanism that determines the chromatin pattern for a particular cell type is the regulation of the quantity and quality of heterochromatin. Specifically, we will demonstrate that this is achieved, in a developmental and tissue specific manner, by changing the make-up of chromosomal domains through the replacement of histone proteins with specialised forms of histones called variants . In addition, we will expose a new mechanism of how heterochromatin formation controls the rate of cellular proliferation. This information will provide new insights into how gene expression profiles are established at precise times in early development, and offer a new strategy to inhibit the proliferation of cancer cells.Read moreRead less
Synthetic regulators of gene expression. RNA plays many essential roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis. Despite these realisations the current approaches to manipulate RNA are limited in many respects. This project will use synthetic biology approaches to engineer synthetic regulators of RNAs in living cells. These studies will provide new tools for use in biological research and provide insights into h ....Synthetic regulators of gene expression. RNA plays many essential roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis. Despite these realisations the current approaches to manipulate RNA are limited in many respects. This project will use synthetic biology approaches to engineer synthetic regulators of RNAs in living cells. These studies will provide new tools for use in biological research and provide insights into how natural proteins control gene expression. Furthermore, this project will use these tools to understand the mechanisms of how proteins are synthesised in mammalian mitochondria.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
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
How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the h ....How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the human counterparts of the Drosophila proteins studied here, function similarly. Benefits will be provided in the form of job creation, and new knowledge in fundamental aspects of life, including brain development and cell fate maintenance.Read moreRead less
The selective elimination of mitochondria from yeast cells: regulation and molecular mechanism . For healthy cells the quality of the mitochondrion, the cellular power plant, must be maintained. The results of this research will contribute to an understanding of the molecular mechanism for the removal of mitochondria from the cell, and ultimately inspire strategies for the treatment of diseases that result from faulty mitochondria.
Discovery Early Career Researcher Award - Grant ID: DE120100782
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Identifying molecular regulators of haematopoietic stem cell development. Blood stem cells are capable of making all types of mature blood cell whilst making new copies of themselves. These properties are essential for the life-long supply of blood and make stem cells ideal for therapeutic use. By studying embryos, this project will identify genes that control the production and expansion of blood-forming stem cells.