A National Resource For Mouse Models Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$483,643.00
Summary
Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resour ....Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.Read moreRead less
I am a clinician-scientist investigating the immunopathogenesis of rhematoid arthritis in order to discover and develop new forms of therapy and prevent disease complications. I am interested in improving patient care through research on patient educatio
We plan to collect health information from Australian patients with arthritis to monitor the benefits and safety of new treatments. All patients being treated with the new injectable biologic agents and other patients taking conventional drugs will be invited to take part in the follow up program. We will measure the impact of arthritis on quality of life and physical function and the long-term effects of all arthritis drugs. This will be of immense value to the Australian community as this data ....We plan to collect health information from Australian patients with arthritis to monitor the benefits and safety of new treatments. All patients being treated with the new injectable biologic agents and other patients taking conventional drugs will be invited to take part in the follow up program. We will measure the impact of arthritis on quality of life and physical function and the long-term effects of all arthritis drugs. This will be of immense value to the Australian community as this data are not routinely available from any other source. It will help rheumatologists and patients make the best decisions regarding long-term arthritis treatments.Read moreRead less
Overcoming Breast Cancer Heterogeneity And Resistance Using A Novel Therapeutic Approach Targeting The Metastasis Suppressor NDRG1.
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancer (BrCa) is the leading cause of cancer death in women and current treatments suffer from development of resistance, leading to metastatic progression. I will assess a novel treatment strategy for BrCa, targeting a gene that is able to inhibit multiple key drivers of BrCa, using a novel potent and selective anti-cancer agent. This approach has the potential to overcome resistance to current therapies and alleviate the onset of metastasis, to improve prognosis for BrCa patients.
Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to ....Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to improve radiotherapy treatments in patients with small lesions with sizes of up to a few centimetres. This will lead to an improved outcome for some cancer patients.Read moreRead less
Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and imp ....Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and improved therapy resulting in higher cure rates and in a dramatic reduction in the cost of treating patients. A novel therapy will provide considerable benefits for the national biotechnology industry.Read moreRead less
TACI: A Novel Immune Checkpoint In Chronic Lymphocytic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$874,462.00
Summary
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. CLL cells actively shut down immune defenses in patients. Moreover, current as well as emerging more targeted therapies suppress immunity and over a quarter of patients will die from an infection despite a good response to cancer treatments. Our laboratory has gained new understanding in the mechanism of action of a new treatment for CLL called Ibrutinib. This information allows us to design improved treatment options for CLL.
Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The ....Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The experience and commitment of the multi-disciplinary network of researchers offers exceptional training and employment opportunities for tomorrow's scientists in techniques for discovery and characterisation of novel chemicals, and their interaction with disease targets.Read moreRead less
Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase ge ....Mammalian chitinases and gene therapy: new weapons to combat fungal and insect attack in mammals. Plants combat fungal and insect attack by producing chitin degrading enzymes. Related, chitinolytic enzymes have been identified in mammals, but their functions are unclear. We found that chitinases from human macrophages inhibited fungal growth. We hypothesise that, like plants, mammalian chitinases are produced to fight chitin containing pathogens. We will transform cells with a chitotriosidase gene and encapsulate them, creating bioreactors secreting chitinases. Therapeutic effects will be tested by grafting bioreactors to mice inoculated with Aspergillus. The research is a new approach to fighting chitin containing pathogens, with potential applications from parasite infestations in livestock to fungal infections in humans.Read moreRead less