Combined Expression Analysis And SNP-based Measurement Of Copy Number Variation In Ovarian Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$440,124.00
Summary
For a woman with advanced ovarian cancer, the degree and duration of her response to platinum agents is probably the single most important determinant of her chance of survival for an extended period. At the moment we cannot accurately predict that response and, despite a great deal of effort, we don't understand what controls her initial response to treatment and almost inevitable relapse with platinum-refractory disease. In recent years it has become possible to measure the patterns of activit ....For a woman with advanced ovarian cancer, the degree and duration of her response to platinum agents is probably the single most important determinant of her chance of survival for an extended period. At the moment we cannot accurately predict that response and, despite a great deal of effort, we don't understand what controls her initial response to treatment and almost inevitable relapse with platinum-refractory disease. In recent years it has become possible to measure the patterns of activity of thousands of genes simultaneously using microfabricated devices known as microarrays. As aberrant gene activity is a major determinant of tumour growth and drug sensitivity, we expect that such information will provide an insight into the dynamics of tumour growth and lead to tests that are predictive of treatment response and survival. Indeed, there are now a number of examples of solid cancers where microarray-based expression information is predictive of outcome and in breast cancer such information is being actively developed as a clinical tool. Our proposed research is based on the Australian Ovarian Cancer Study (AOCS), which is a national study established in January 2003 through a US Department of Defense CDMRP-OCRP Program grant. In just over 24 months AOCS has become the largest study of its kind in the world and represents a powerful bioresource for the molecular analysis of ovarian cancer. The objective of this application is to extend microarray analysis of AOCS serous ovarian cancer cases, particularly focusing on women with primary and acquired platinum resistance. Platinum resistance is the major barrier to long-term remissions in women with ovarian cancer. High-resolution genomic analysis of a large number of well-selected cases with linked outcome data should provide an extremely valuable molecular dataset for ovarian cancer.Read moreRead less
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.
New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
It has become increasingly evident that damage to the genetic material in cells (DNA) is a fundamental initiating cause of cancer and accelerated ageing. Furthermore it has been shown recently that moderate deficiencies of certain vitamins and minerals can cause damage to DNA at a level that is observed for carcinogenic doses of radiation and toxic chemicals. In addition studies have shown that supplementation with certain vitamins resulted in a reduction of damage to DNA. The aims of this resea ....It has become increasingly evident that damage to the genetic material in cells (DNA) is a fundamental initiating cause of cancer and accelerated ageing. Furthermore it has been shown recently that moderate deficiencies of certain vitamins and minerals can cause damage to DNA at a level that is observed for carcinogenic doses of radiation and toxic chemicals. In addition studies have shown that supplementation with certain vitamins resulted in a reduction of damage to DNA. The aims of this research is to determine whether daily intake of a pill containing certain vitamins and minerals causes a reduction in DNA damage in blood cells. The expected ultimate outcome is a cancer prevention strategy based on reducing the risk of damage to DNA.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulatio ....Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulation of non-coding transcripts and genomic instability. This work aims to understand eukaryotic genome organisation and may have long-term therapeutic implications for cancer and ageing-related diseases.Read moreRead less
A Genome-wide Association Study Of Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,066,328.00
Summary
Endometrial cancer (uterine-womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition. The non-biased approach of our large study will identify genes that increase risk of this cancer, to provide information for future targeted therapies to prevent progression, and large-scale studies investigating how these genes interact with environmental factors such as hormone replacement therapy and obesity to cause disease.
Discovery Early Career Researcher Award - Grant ID: DE120102763
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The contribution of histone post-translational modifications to eukaryotic evolution. By comparing the complete DNA sequence of closely related species, it is possible to identify changes in DNA that account for the diversity between these species. The project will use this approach to ask whether DNA changes that influence how DNA itself is packaged into cells have contributed to the evolution of new yeast species.