Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide ....Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide a short-cut to the cloning of one such gene. We have started with the mouse version, which is lost in leukemic cells. We have mapped the gene to within a very small chromosomal region, and we have identified a biological effect which correlates with loss of the gene. Our next step is to combine these two approaches to clone the gene. Because these genes are always highly conserved between species, we will be able to quickly clone the corresponding human gene, the loss of which is very likely to be important in cancer of various types.Read moreRead less
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
Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.
Treatment Of Genetic Liver Disease By Homologous Recombination In Vivo, Coupled With A Pharmoco-genetic Strategy For Selective Expansion Of Genetically Repaired Hepatocytes
Funder
National Health and Medical Research Council
Funding Amount
$920,836.00
Summary
This project seeks to exploit recent advancements in our ability to precisely “edit” and correct mutations underlying human genetic diseases. To improve therapeutic efficiencies of the system, we will deliver the technology using highly efficient virus-based systems and apply a novel post-repair selection process to preferentially repopulate the liver with gene-repaired cells. Demonstration of the strategy in a humanised mouse model will provide important preclinical data for human applications.
Molecular Analyses Of Flavivirus RNA Replication, Encapsidation, And Complementation
Funder
National Health and Medical Research Council
Funding Amount
$602,545.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are ....Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our understanding of how the flavivirus RNA replication complex is assembled, how it synthesizes RNA and how this RNA is specifically packaged to produce infectious virus. To achieve these goals we will employ state-of-the-art molecular biology techniques based on manipulations with infectious complementary DNA copy of Kunjin virus RNA. The intimate understanding of these mechanisms in flavivirus replication should facilitate the design of efficient antiviral drugs by specifically targeting unique events in RNA replication and-or packaging. This may assist in the development of antiviral drugs for treatment of infections caused by other higly pathogenic flaviviruses in Australia, such as dengue, Japanese encephalitis and Murray Valley encephalitis, as well as of the related heptitis C virus.Read moreRead less
Understanding The Genetic Basis Of Breast Cancer: Translation To Primary And Secondary Prevention
Funder
National Health and Medical Research Council
Funding Amount
$2,731,372.00
Summary
We have identified >200 regions of the genome that contain variants that increase breast cancer risk. I will now focus on the main challenges i.e. to a) find the remaining genetic risk factors that will collectively explain all of the genetic risk, b) understand how these work, in particular which genes they influence and c) apply this knowledge to find and develop new drugs. Importantly, such drugs could be used not only to treat breast cancer, but also to prevent it in high-risk women.
Site-specific Integration Of Functional Genomic Loci: Applications In Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$442,664.00
Summary
Gene therapy strategies have traditionally focused on the delivery of therapeutic genes by viral vectors. Mindful of the limitations and potential problems of viral gene delivery, non-specific viral integration and limited transgene expression, this investigation will explore the delivery and site-specific integration of large genomic fragments into human stem cells. It is anticipated this approach will avoid some of the problems associated with poor gene expression and insertional oncogenesis.
I aim to decipher the role of heritable, genetic DNA variation in human neurological disease. I will use next generation genomics technologies together with sophisticated cellular models to address the important questions of the biology of epilepsy and intellectual disability in particular. I aim to develop a treatment for a specific type of epilepsy, which affects only girls from the age of 6 months. My ultimate goal is to improve the life of the patients and their relatives.