Broad Spectrum Inhibition Of An Enzyme Antibiotic Target
Funder
National Health and Medical Research Council
Funding Amount
$321,534.00
Summary
There is a well-documented need to replenish the antibiotic pipeline with new products to combat the rise of drug resistant bacteria. In this project, the enzyme dihydrodipicolinate synthase (DHDPS) is targetted which is essential to bacterial viability. A number of independent but synergistic drug discovery approaches are investigated to develop and test DHDPS inhibitors in the pursuit of a novel class of antibiotics.
Biochemical Analysis Of Akt 3-specific Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$349,375.00
Summary
The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific a ....The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific antibody, we find Akt 3 protein and activity levels are high in rapidly proliferating ovarian cancer cell lines and in primary ovarian tumours. The aim of this proposal is to characterise the mode and role of signalling via Akt3, including the identification of targeted substrates and signaling pathways and the outcomes of Akt3 driven signaling on cellular properties. These studies will provide important clues to understanding how this family member functions in both health and disease. Elucidation of the basis of Akt3 dependent signalling will open the possibility for the development of drugs that interfere with Akt3 function (for example in high Akt 3 expressing tumours like those of the ovary). In the long term, extension of our profiling studies to other tumour types will give a novel insight into the extent of Akt3 de-regulation as a key mediator of cancer formation.Read moreRead less
The Activation Of Lipoprotein Lipase By Apolipoprotein C-II
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Abnormalities in blood lipid levels are common in our society. Treatment of these conditions adds a heavy burden to national health-care costs. Lipoprotein lipase is a plasma enzyme that plays a central role in maintaining safe blood lipid levels. The action of lipoprotein lipase in subjects on a western diet leads to the hydrolysis of about 150g of plasma triacylglycerol daily. Naturally occurring mutations in lipoprotein lipase, associated with a complete loss of enzyme activity, result in a h ....Abnormalities in blood lipid levels are common in our society. Treatment of these conditions adds a heavy burden to national health-care costs. Lipoprotein lipase is a plasma enzyme that plays a central role in maintaining safe blood lipid levels. The action of lipoprotein lipase in subjects on a western diet leads to the hydrolysis of about 150g of plasma triacylglycerol daily. Naturally occurring mutations in lipoprotein lipase, associated with a complete loss of enzyme activity, result in a high blood-lipids that can lead to premature atherosclerosis. Regulation of lipoprotein lipase occurs via an interaction with the regulatory protein apolipoprotein C-II. Individuals with apolipoprotein C-II deficiency also exhibit abnormal plasma lipid levels with an associated increased risk of coronary heart disease. These considerations demonstrate that the activation of lipoprotein lipase by apolipoprotein C-II is pivotal to the maintenance of normal blood lipid levels. The present proposal will establish the structure and orientation of apolipoprotein C-II in a lipid environment and provide a structural model for the activation of lipoprotein lipase by apolipoprotein C-II. These molecular details will serve as a model for the regulatory interactions of other apolipoproteins within lipoprotein particles and will generate leads for the development of new strategies for the treatment of blood lipid irregularities.Read moreRead less
Viral capsids as high-efficiency nanoreactors. This project aims to develop state-of-the-art single-molecule imaging to visualise DNA synthesis inside authentic retroviral capsids in real time. The project expects to generate new knowledge in the fields of virology, synthetic biology, and nanotechnology by utilising cutting-edge fluorescent labelling reagents and microscopy technology. Expected outcomes include a comprehensive description of retrovirus reverse transcription, development of innov ....Viral capsids as high-efficiency nanoreactors. This project aims to develop state-of-the-art single-molecule imaging to visualise DNA synthesis inside authentic retroviral capsids in real time. The project expects to generate new knowledge in the fields of virology, synthetic biology, and nanotechnology by utilising cutting-edge fluorescent labelling reagents and microscopy technology. Expected outcomes include a comprehensive description of retrovirus reverse transcription, development of innovative biophysical techniques for the study of viruses, and an understanding of the engineering principles at play in natural nano-reactors. This project anticipates contributing advanced capabilities in bionanotechnology, benefiting therapeutic, biotechnology and synthetic biology applications.Read moreRead less