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.
Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches ....Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches for protein production and to apply them to the analysis of the basic mechanisms of cell self-maintenance.Read moreRead less
NmlR-dependent thiol-based redox systems and their role in global stress responses in bacteria. All cells sense changes to their environment and respond by altering their metabolism. A major environmental change is oxidative stress which damages cells. Cells have the ability to sense oxidative stress and alter metabolic processes to defend against the damage that it elicits. This proposal will characterize a novel oxidative stress defense system that is found in a number of bacterial pathogens t ....NmlR-dependent thiol-based redox systems and their role in global stress responses in bacteria. All cells sense changes to their environment and respond by altering their metabolism. A major environmental change is oxidative stress which damages cells. Cells have the ability to sense oxidative stress and alter metabolic processes to defend against the damage that it elicits. This proposal will characterize a novel oxidative stress defense system that is found in a number of bacterial pathogens that need to defend themselves against attack by the host. The project may identify new ways to manage these bacterial pathogens. It may also provide an insight into oxidative stress defense processes that are linked to pathologies in humans.Read moreRead less
The role of human single stranded DNA binding protein 1 in the repair of stalled DNA replication forks. It is vital that human cells protect their genetic code in order to prevent cancer. This project will look at how cells do this, with the aim of finding new ways to protect us from cancer.
Redirecting Carbon Flow through Mesophyll and Bundle Sheath Cells of Sugarcane to Produce Poly-3-Hydroxybutyrate. This project is part of the National Priorities "Frontier Technologies for Building and Transforming Australian Industries." Using innovative plant metabolic engineering technologies combined with sophisticated computer modeling we are generating green plants that produce renewable, biodegradable, bioplastics possessing properties such that they are suitable replacements for petrol ....Redirecting Carbon Flow through Mesophyll and Bundle Sheath Cells of Sugarcane to Produce Poly-3-Hydroxybutyrate. This project is part of the National Priorities "Frontier Technologies for Building and Transforming Australian Industries." Using innovative plant metabolic engineering technologies combined with sophisticated computer modeling we are generating green plants that produce renewable, biodegradable, bioplastics possessing properties such that they are suitable replacements for petroleum-derived products in many applications. During the course of these studies, we are increasing our basic level of understanding of plant metabolism of important bioenergy crops. The production of renewable, bioplastics in sugarcane will help to diversify the Australian sugarcane industry by providing a value-added product with significant world-wide markets.Read moreRead less
Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights ....Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights into endosomal trafficking at the molecular level. Outcomes from this work will place Australia at the forefront of international efforts to understand this essential biological process and will have important implications for future design of pharmaceuticals.Read moreRead less
Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis tha ....Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis that changes in the RNA-binding protein composition of cholesterol-rich membranes mediate the selection of miRNA loaded in the vesicles. This knowledge may increase our understanding of mechanisms of disease because this mode of cell-to-cell communication is disrupted or hijacked in pathologies. Future translation in diverse applications may improve human, animal and plant health.Read moreRead less
Acquisition of the mitochondrial genome restores mitochondrial function. The aim of this project is to show that cancer cells with heavily damaged mitochondrial DNA (mtDNA) can acquire the mitochondrial genome from the host and that this results in the recovery of their mitochondrial function. The project is highly significant, as it aims to show in vivo mitochondrial transfer with functional consequences. The project aims to open a new avenue of research and could result in a shift in our under ....Acquisition of the mitochondrial genome restores mitochondrial function. The aim of this project is to show that cancer cells with heavily damaged mitochondrial DNA (mtDNA) can acquire the mitochondrial genome from the host and that this results in the recovery of their mitochondrial function. The project is highly significant, as it aims to show in vivo mitochondrial transfer with functional consequences. The project aims to open a new avenue of research and could result in a shift in our understanding of some features of cellular communication and how cells can overcome unfavourable situations.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less