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
Characterising The Physiological Roles Of The Asparaginyl Hydroxylase FIH-1 In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$274,743.00
Summary
FIH-1 is an oxygen-sensing protein expressed in every cell. The ability for cells to detect and respond to oxygen deficiency is necessary for survival in heart disease and stroke, and is also a feature of cancer. This research aims to characterise the role FIH-1 plays in normal development and disease using mouse and tumour model systems. This research could ultimately indicate whether FIH-1 is a feasible drug target.
Characterization Of A Novel Secretion And Attachment System Necessary For The Formation Of A Virulence Coat In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$828,857.00
Summary
In this study we will characterize a novel bacterial secretion system that we have discovered. This system mediates the secretion of proteins from the bacterial cell and their attachment to the cell surface. This system is essential for the virulence of a bacterium associated with severe gum disease. The chacterization of this system may offer opportunities for the development of new treatments to target this disease.
Heterogeneity In Processing And Signalling By The Notch Family Of Receptors In Vascular Development And Remodelling.
Funder
National Health and Medical Research Council
Funding Amount
$85,716.00
Summary
Formation and remodelling of the blood vessels is a critical feature of development. In addition, numerous disorders including psoriasis, arthritis, blindness, heart and brain ischemia, neurodegeneration, hypertension, pre-eclampsia, respiratory distress and osteoporosis among others are characterised by defective blood vessel patterning. The significance associated with understanding how Notch genes direct blood vessel formation is paramount, as this knowledge will inform future research.