Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiati ....Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiating (stem cell) property of tumour cells is maintained offers potential novel avenues to eliminate persistent cancer cells. This knowledge will ultimately lead to better management and treatment of cancer, and increase survival. An understanding of stem cell behaviour is also central to the control of degenerative conditions.Read moreRead less
The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its developmen ....The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its development are unknown. This project aims to better understand the critical first step in the progression to cancer and thus expand the scope for the development of therapies, particularly those aimed at early intervention, and tools that predict progression.Read moreRead less
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.
Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will th ....Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will then be able to be tested for their ability to act as specific drug delivery systems for use in the treatment of solid tumours.Read moreRead less
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
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.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
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA fro ....Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA from large numbers of tumours is essential to identify and understand the combinations of cancer mutations that are most deadly. Such studies can form the basis for developing better diagnostics and new treatments for patients whose tumours are resistant to current therapies.Read moreRead less