Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated c ....Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated cancer cells. This will provide the basic information for drug discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The e ....Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The economic and social impact is immense, placing a huge strain on the healthcare system, as well as on the families affected. Any alternative treatment reducing cancer metastasis would be of enormous national and international benefit. It's believed that the significant studies outlined in this proposal, which are based on exciting preliminary data, will make a sizeable contribution to achieving this goal.Read moreRead less
Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can sea ....Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can search for, identify and study the function of many of the downstream signalling proteins in activated cancer cells. This will provide the basic information for discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less
Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will deciphe ....Characterisation of molecular regulation of telomerase and telomeres by p53 in cell ageing. Telomeres, the ends of chromosomes shorten as a function of cell division, and thereby limit cell lifespan. Telomerase synthesizes telomeres and thus renders cells immortal. Recently, we found that p53, a protein with an important role in cell aging and in the uncontrolled growth of cancer, interacts with telomeres and telomerase by binding to the telomere proteins TRF1 and TRF2. This project will decipher the mechanisms by which p53 regulates telomerase and telomeres, and establish the interrelationship of these proteins in regulating cell lifespan, death and immortalisation. It will provide important information for molecular intervention in cell ageing and immortalisation.Read moreRead less
DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on b ....DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on blood or bodily excretions, and to pursue novel therapeutic approaches for treating cancer. The expected outcomes would generate exports to markets in the USA and Europe and replace imports of drugs and technology to treat cancer.Read moreRead less
Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. O ....Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. Our goal is to identify those cells and to determine which genes are involved in transforming a normal cell to a cancerous cell.Read moreRead less
New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways res ....New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways responsible for how a cell manages stress by regulating levels of proteins involved in the cellular stress response. Discoveries made during the course of this research will provide knowledge of gene and protein interactions that will be important in the future to develop anti-cancer therapies. Read moreRead less
Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both with ....Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both within and outside the nervous system, ultimately leading to preventative and restorative strategies for maintaining good health. Finally, this Proposal is of significant national benefit as it will undoubtedly advance our knowledge base in stem cell biology, helping to maintain Australia as a global leader in stem cell research.Read moreRead less