Identification Of Orphan F-box Helicase Substrates And Their Role In Genomic Stability And Life Extension.
Funder
National Health and Medical Research Council
Funding Amount
$281,684.00
Summary
Within each cell proteins are synthesised and destroyed with delicate control to ensure the cell functions appropriately. Excess proteins are removed by specific degradation pathways, which are often misregulated in cancer. This project aims to further our understanding of misregulated protein degradation in cancer. The knowledge gained will assist with the development of cancer targeting drugs specific to protein degradation pathways that become misregulated in tumour formation.
The future of cancer therapy lies in the tailoring of treatment to the characteristic of individual tumour. We have previously identified a subset of breast tumours that are characterised by the presence of large excess of proteins called D-type cyclins. Similar overexpression of cyclin D1 has been shown to lead to the development of cancer in mammary gland in animal models. In normal cells, D-type cyclins are degraded rapidly, therefore the regulation of protein degradation, or proteolysis, is ....The future of cancer therapy lies in the tailoring of treatment to the characteristic of individual tumour. We have previously identified a subset of breast tumours that are characterised by the presence of large excess of proteins called D-type cyclins. Similar overexpression of cyclin D1 has been shown to lead to the development of cancer in mammary gland in animal models. In normal cells, D-type cyclins are degraded rapidly, therefore the regulation of protein degradation, or proteolysis, is crucial in preventing the accumulation of D-type cyclins. In the subset of breast cancers we have identified, D-type cyclin proteolysis is defective. We, and others, have obtained evidence for the involvement of the SKP2 gene in the proteolysis of D-type cyclins. SKP2 has also been shown to be required for the proteolysis of another important protein, called p27. In the clinic, accumulation of p27 in tumours is used as a good prognostic indicator. However, some exceptions have been found where the accumulation of p27 correlates with aggressive tumours. As D-type cyclins are able to counteract the effect of p27, we hypothesise that the aggressive behaviour of these tumours is due to the simultaneous accumulation of D-type cyclins and that this is due to a mutation in the SKP2 gene. The experiments described in this proposal are designed to test this hypothesis. As the choice of treatment is affected by the interpretation of p27 levels, the results obtained from this study may have a direct impact in the clinic.Read moreRead less
Studies of Group 15 complexes of the Lanthanoids and Group 2 metals-An unexploited field of research. The project will initially explore new amido chemisty of the lanthanoids. This chemistry will develop towards complexes with lanthanoid-or Group 2-phosphorus, -arsenic, -antimony or -bismuth connectivities. This chemistry is surprisingly underdeveloped given the wealth of applications found for oxo and amido complexes of the same metals. Structural studies involving the complexes using cutting e ....Studies of Group 15 complexes of the Lanthanoids and Group 2 metals-An unexploited field of research. The project will initially explore new amido chemisty of the lanthanoids. This chemistry will develop towards complexes with lanthanoid-or Group 2-phosphorus, -arsenic, -antimony or -bismuth connectivities. This chemistry is surprisingly underdeveloped given the wealth of applications found for oxo and amido complexes of the same metals. Structural studies involving the complexes using cutting edge ligands will reveal interesting coordination modes. The discovery of new reaction pathways will be of interest to the wider chemical community. The chemical reactivity and potential catalytic or luminescent properties of these compounds will be studied and will result in publications in international journals.Read moreRead less
New approaches to bistable spin clusters. Future advances in data storage technology and other areas of electronics depend on the miniaturisation of the relevant components. The goal of this project is to create materials where individual molecules can be the units of magnetic memory for high density data storage or the switches in electronic devices. Fundamental research in these areas is being pursued vigourously overseas and Australian involvement through this project is important for the p ....New approaches to bistable spin clusters. Future advances in data storage technology and other areas of electronics depend on the miniaturisation of the relevant components. The goal of this project is to create materials where individual molecules can be the units of magnetic memory for high density data storage or the switches in electronic devices. Fundamental research in these areas is being pursued vigourously overseas and Australian involvement through this project is important for the possibility of local development of devices based on the new materials. The students and postdoctoral fellows involved in this work will receive world class training in the synthetic and physical techniques that underpin the emerging fields of molecular magnetism and molecular electronics.Read moreRead less
Novel Lanthanide Complexes and Polymeric Luminescent Chelates for Biomedical Imaging and Bioassay. The development of advanced materials and frontier technologies such as the luminescent chelates proposed here is essential for Australia's evolution as a competitive nation in fields such as biomedical imaging and clinical diagnostics. For example, the total expenditure on fluorescent reagents in 2004 exceeded US$1.5 billion, with an estimated 25% annual growth. With proven applications in diagnos ....Novel Lanthanide Complexes and Polymeric Luminescent Chelates for Biomedical Imaging and Bioassay. The development of advanced materials and frontier technologies such as the luminescent chelates proposed here is essential for Australia's evolution as a competitive nation in fields such as biomedical imaging and clinical diagnostics. For example, the total expenditure on fluorescent reagents in 2004 exceeded US$1.5 billion, with an estimated 25% annual growth. With proven applications in diagnostic immunoassay and high throughput screening, the use of luminescent lanthanide complexes allows significant improvements over traditional fluorophores, facilitating miniaturisation and ultimately leading to reduced costs for the consumer.Read moreRead less