Genome-wide SNP Analysis Of Fibroblasts Juxtaposed Or Distant From Epithelial Breast And Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$401,763.00
Summary
In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal t ....In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal tissue surrounding the cancer (often referred to stroma) may also contain mutations. This so called 'cancer associated stroma'(CAS) is also thought to harbour genetic mutations and some studies have shown that without these mutations the cancer cannot survive. At present we have only had glimpses of the genetic alterations that may occur in CAS and there is an urgent need to fully understand the interplay between CAS and frankly cancerous tissue. Our laboratory will utilise high density, genome-wide screening technologies to search for novel mutations in CAS from breast and ovarian cancers. A complete understanding of the role stroma plays in cancer development is likely to lead to novel ways of treating and preventing cancer. Consequently, the identification of the full repertoire of stroma-derived cancer promoting genes is emerging as one of the most important areas in cancer research. The identification of these genes could lead to the development of novel diagnostic markers for use in cancer detection, diagnosis and-or prognosis.Read moreRead less
High Resolution Genome-wide SNP Analysis Of Genetic Alterations In Early Ovarian Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$587,055.00
Summary
Ovarian cancer is the 5th leading cause of cancer death in women. For such a significant disease, remarkably little is know about its origins and this has limited progress in developing more effective diagnostic markers. We will undertake cutting edge genome-wide analysis of pre-invasive ovarian tumours to identify genetic markers relevant to malignancy. This work will significantly expand our understanding of how ovarian cancers develops.
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.
Identification Of Breast And Ovarian Tumour Suppressor Genes On Chromosome 22 By Functional Complementation
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor ....Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor genes exist in the human genome and of these only a small proportion have been identified. The aim of this study is to identify genes on human chromosome 22 that are involved in the development of breast and ovarian cancer. Genetic evidence from many investigators, including data from our own laboratory, has indicated that multiple tumour suppressor genes are present on human chromosome 22 but as yet none have been positively identified. Part of the difficulty in identifying these genes is that cancer cells often have a lot of genetic damage and it is hard to distinguish the important changes from background genetic noise'. To circumvent this problem we are using a functional cloning approach which identifies tumour suppressor genes by their ability to inhibit the growth of cancers cells grown in culture in the laboratory. Genes that are identified in this way will be evaluated for the presence of genetic mutations in real human cancers which will give us a better idea of their true significance in tumour development. In addition to enhancing our understanding of the process tumour development this project may identify new targets for anti-cancer therapies.Read moreRead less
Physiological Genomic Analysis Of Lvm-1 - A Genetic Locus That Determines Left Ventricular Mass
Funder
National Health and Medical Research Council
Funding Amount
$356,540.00
Summary
As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on ra ....As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on rat chromosomes that harbour the gene or genes that influence heart size. The aim of these studies is to identify the exact gene responsible and to understand how that gene produces its effects. The experiments involve testing DNA samples already obtained from many hundreds of rats and breeding animals to study the consequences of the genetic abnormality in greater detail. The experiments are critical steps towards the prevention of big hearts and their complications in humans. In time, genetic tests will offer earlier detection and facilitate targeted and tailored treatments.Read moreRead less
Genetic Analysis Of Type 2 Diabetes In Indigenous Australian Pedigrees.
Funder
National Health and Medical Research Council
Funding Amount
$502,500.00
Summary
Type 2 diabetes is a major world health problem. With 300 million people expected to be affected worldwide by 2025 it is a major economic burden. It is a leading cause of kidney failure, blindness, heart attacks, strokes and amputations. Over 7% of the general Australian population have type 2 diabetes, whilst up to 30% of the population in some indigenous communities are affected by this condition. Very few Australians have not been touched in some way by the shadow of diabetes. The precise cau ....Type 2 diabetes is a major world health problem. With 300 million people expected to be affected worldwide by 2025 it is a major economic burden. It is a leading cause of kidney failure, blindness, heart attacks, strokes and amputations. Over 7% of the general Australian population have type 2 diabetes, whilst up to 30% of the population in some indigenous communities are affected by this condition. Very few Australians have not been touched in some way by the shadow of diabetes. The precise cause of diabetes is unknown, however we do know that it tends to run in families, indicating that inherited tendency is important. This research program will find genes which cause diabetes by searching for them in indigenous Australian pedigrees in which many of the family members are affected by diabetes. Finding the genes which cause diabetes will have significant impact in at least three major ways. Firstly, it will increase our understanding of the disease process. Secondly, it will be possible to develop tests to identify people at risk of diabetes at a very early stage so that therapy can be introduced and complications averted. Thirdly, it will be possible to develop new and more effective approaches for the prevention and treatment of type 2 diabetes.Read moreRead less
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.