High Resolution Genome-wide Genomic Analysis Of DCIS To Identify Genes Involved In Disease Initiation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$543,370.00
Summary
DCIS is the most common type of noninvasive breast cancer and in some women may progress to malignant disease but little in know about how it develops. We will bring to bear our experience with cutting edge technology and access to extensive clinical resources to the analysis of a large series of pure DCIS with the aim of identifying previously unknown cancer causing genes. This data will lead to the identification of novel breast cancer genes that will assist clinical management.
Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, ....Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.Read moreRead less
Induction Of Reactive Oxygen Species By Hepatitis C Virus And Its Role In Liver Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that vira ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that viral proteins and viral replication play in the development of liver disease are not well characterized. Previous experiments in the laboratory have shown that one of the hepatitis C virus proteins results in the formation of toxic oxygen molecules known as a reactive oxygen species. This toxic oxygen molecules can have an effect on liver cells that may enhance the progression of the liver disease process in hepatitis C virus infected individuals. The role that these molecules play in liver cells is unknown but experiments are planned in laboratory model systems and in specimens obtained from hepatitis C virus infected individuals to further examine potential mechanisms. This will hopefully lead to the identification of new treatments for hepatitis C virus liver disease. Some patients with hepatitis C will develop liver cancer, however, all the reasons are not known. Using new technology known as microarray, a consequence of the human genome project, we have been able to look at the expression levels of thousands of genes in liver cancer. Experiments are planned to determine if these genes are important in liver cancer and if they can be used as targets for therapy or to more easily diagnose liver cancer.Read moreRead less
Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
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.
Fine Scale Mapping And Identification Of The IBD1 Gene On Chromsosome 16
Funder
National Health and Medical Research Council
Funding Amount
$483,849.00
Summary
One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more th ....One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more than 10,000 Australians who suffer from IBD. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is complex, resulting from the interaction of a number of different genes. To date, one genetic localisation on chromosome 16 has been established in several different populations, and we have confirmed the importance of this localisation in the Australian population. We will further refine the localisation by fine scale mapping in the pericentromeric region of chromosome 16 by identifying and studying the inheritance of novel markers in the region. We will then identify and characterise the gene itself using several complementary appoaches that rely on differences at the molecular level between disease and normal tissue. This work is part of the international effort to identify all IBD susceptibility genes. Once that is achieved, approaches to explaining the interactions between the genes, their protein products and environmental triggers can be determined. Only when the mechanisms of these interactions are understood will the expectation of rational therapies based on an understanding of disease aetiology be possible.Read moreRead less