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Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity ....Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity, insulin resistance and various forms of cancers is well established) are leading to a rapid increase in new cancer cases, thus driving a rapid increase in demand for better treatments. This is particularly relevant in Indigenous health where obesity is on the rise following the transition from a traditional to an urban lifestyle.Read moreRead less
Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways m ....Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways may lead to a novel methodology to activate silenced genes as well as determine the role of ncRNAs in genome evolution.Read moreRead less
Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally inf ....Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally infected or oncogenically transformed cells. Outcomes of this work may contribute to development of novel anti-cancer and anti-viral therapies, diagnostic reagents and vaccines.Read moreRead less
Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Progr ....Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Programmed Cell Death. This information is critical for the development of drugs designed to re-initiate Programmed Cell Death in cancer cells.Read moreRead less
Ambient spatial intelligence: Spatial analysis and event detection in environmental geosensor networks. This project will design and test innovative new decentralised algorithms for responding to spatiotemporal queries in environmental monitoring networks. The research is essential for constructing larger, denser, and more reliable networks, helping to embed spatial intelligence within the environment itself (ambient spatial intelligence). The project builds on Australia's existing research exce ....Ambient spatial intelligence: Spatial analysis and event detection in environmental geosensor networks. This project will design and test innovative new decentralised algorithms for responding to spatiotemporal queries in environmental monitoring networks. The research is essential for constructing larger, denser, and more reliable networks, helping to embed spatial intelligence within the environment itself (ambient spatial intelligence). The project builds on Australia's existing research excellence in geographic information science. By making smarter use of spatial information, the project will further strengthen Australia's world-leading spatial information industry, and support sustainable and economic environmental management through important applications like conservation contracts and carbon sequestration monitoring.Read moreRead less
Long noncoding RNAs and their regulatory roles in epigenetic control of gene expression in plants. Epigenetic control of gene expression plays a critical role in development, environmental adaptation, stress response and disease resistance in plants, but its molecular basis remains largely unknown. The proposed study should contribute to the emerging field of epigenetics by discovering new regulatory noncoding RNAs involved in epigenetic mechanisms in plants. These new discoveries could potentia ....Long noncoding RNAs and their regulatory roles in epigenetic control of gene expression in plants. Epigenetic control of gene expression plays a critical role in development, environmental adaptation, stress response and disease resistance in plants, but its molecular basis remains largely unknown. The proposed study should contribute to the emerging field of epigenetics by discovering new regulatory noncoding RNAs involved in epigenetic mechanisms in plants. These new discoveries could potentially provide new opportunities and platforms for improving the performance, yield and quality of crop plants. The proposed study is therefore consistent with the national research priority goals such as breakthrough science, frontier technologies and promoting an innovation culture.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene exp ....Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene expression data supports homology between sponge and eumetazoan tissues and body plans. This project could illuminate the evolutionary history of the animal body plan.Read moreRead less
Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides ....Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and new tools for Australian industries.Read moreRead less