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Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for can ....Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for cancer treatment.Read moreRead less
It is seldom the initial cancer that kills the patient; most deaths are due to its metastatic spread throughout the body. Survival after the onset of a brain metastasis is dismal. Current understanding of cancer spread to the brain is poor and yet an ability to inhibit this process would save thousands of lives each year. Using rare tissue resources and cutting-edge technologies, this project will elucidate molecular features of brain metastases that can be exploited to generate new treatments.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
Rad50 Protects The Integrity Of The Genome To Minimise Disease Risk
Funder
National Health and Medical Research Council
Funding Amount
$524,222.00
Summary
Exposure to both endogenous products of metabolism as well as a variety of exogenous agents (UV, X-rays) increases the risk of cancer and other diseases. This project is designed to further investigate a novel defect in the Rad50 gene that predisposes to genetic instability and cancer. In short we have described for the first time a patient with a defect in the Rad50 gene. This information will assist in understanding our defence systems against oxidative stress to reduce the risk of disease.
Mechanistic And Functional Characterization Of The Atypical Kinase SgK269
Funder
National Health and Medical Research Council
Funding Amount
$271,879.00
Summary
The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast ....The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast cancers.Read moreRead less
Molecular Characterisation Of Telomere Trimming And Its Role In Cell Proliferative Capacity
Funder
National Health and Medical Research Council
Funding Amount
$403,439.00
Summary
Telomeres are protective structures at the ends of chromosomes. Telomere length is a major determinant of how many times a cell can proliferate. We have recently discovered a rapid telomere shortening process that we have called telomere trimming. We will analyse the molecular details of this process to determine whether it could be used to shorten telomeres and stop cancer cell proliferation, and whether blocking it could increase cell proliferation in patients with short telomere syndromes.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
The Pez-TGFbeta-miR200-ZEB1-2 Axis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A feature of late-stage cancer is metastasis - the dissemination of cancer cells to other tissues. Despite advances in treatment of primary cancers, metastatic disease remains the major cause of death in cancer patients. In metastatic cancers, the cells undergo a change that enables them to initially invade the surrounding tissues. We have discovered a novel regulator of the invasive process in tissue culture and this study aims to substantiate its role in breast cancer.
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Investigating Signalling Pathways That Mediate Suppression Of Anoikis By Chemokine Receptors In Metastatic Breast Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
This research aims at understanding the "nuts and bolts" of the main killer in cancer patients - tumour metastasis. We will look for molecules that are specific to metastatic tumour cells that transmit signals from the cell surface to the cell "suicide" machinery and prevent metastatic cancer cell death.