INVESTIGATIONS INTO THE BIOLOGICAL FUNCTIONING AND PROGNOSTIC VALUE OF NOVEL METASTATIC MARKERS FOR BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Breast cancer is the most malignant tumour of women and, despite great advances in detection and treatment, some 30% of women who present with primary breast cancer eventually relapse or die of their disease. Genetic studies have resulted in the rapid identification of the one-third of women at high risk of developing breast cancer because of a family history of the disease: it is hoped that these women will eventually benefit from advances in gene therapy now being developed. For the majority o ....Breast cancer is the most malignant tumour of women and, despite great advances in detection and treatment, some 30% of women who present with primary breast cancer eventually relapse or die of their disease. Genetic studies have resulted in the rapid identification of the one-third of women at high risk of developing breast cancer because of a family history of the disease: it is hoped that these women will eventually benefit from advances in gene therapy now being developed. For the majority of women developing breast cancer, however, the outcome, or prognosis, remains uncertain. The most important indicators of outcome are obtained by study of the excised cancer tissue, and these relate to the speed of growth of the cancer cells and their ability to migrate, or metastasise, to other sites in the body. Studies of cancer tissue using molecular cell biological methods has enabled the identification of several markers that are proving useful as indicators of outcome, and further understanding of the biological functioning of these markers will enable these molecules to be targetted in new treatments aimed at preventing the spread of the cancer. The present study will examine the appearance of new markers for cell migration among breast cancers and measure their value as indicators of outcome. One molecule in particular may be useful as a therapeutic target since it is used by migrating cells during development but is not expressed by normal (non-cancer) adult tissue cells. Towards this, the project will seek to understand how this molecule functions in cell migration.Read moreRead less
Mitochondrial Quality Control In Parkinson’s Disease: The Molecular Mechanisms Of PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$558,721.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two genes that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
Molecular Characterisation Of The DBHS Proteins In Telomerase Assembly
Funder
National Health and Medical Research Council
Funding Amount
$686,246.00
Summary
Telomerase is an enzyme that is active in over 90% of cancers. Telomerase activity allows cancer cells to divide an indefinite number of times. We have identified a novel role for the DBHS protein family in regulating telomerase activity. We aim to investigate the mechanisms by which these proteins function to assemble and transport telomerase to its site of action in the cell. We then aim to develop chemical inhibitors of these proteins, and test their utility in preventing cancer cell growth.
This project investigates the way in which viruses are able to use host cell machinery to make viral proteins and to replicate their own genetic material. We focus on the picornavirus family that cause illnesses with important health and economic consequences including serious heart infections such as myocarditis and pericarditis as well as the "common cold". This research we will reveal new possible avenues of antiviral development.
Structure And Function Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$1,282,475.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Molecular Dissection Of The Munc18c:Syntaxin4 Complex Required For Insulin-regulated Exocytosis In Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$601,008.00
Summary
When blood glucose levels are high, insulin signals to fat and muscle cells to remove glucose from the blood. The uptake of glucose relies on membrane fusion events that deliver a specific glucose transporter protein to the cell surface in response to insulin signals. This process is affected in Type II diabetes. Our research will characterise the regulation of these membrane fusion events and will be important for understanding how insulin signals are communicated in health and disease.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.
Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.