Activation Of BMP4 Signalling To Inhibit Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$748,742.00
Summary
The spread of cancer cells to other organs is a common cause of breast cancer-related death in women. Current therapies for advanced breast cancer are often palliative since the secondary tumours become resistant to the chemotherapy. Here, we are using preclinical models of advanced breast cancer to develop a treatment that should be effective in patients with secondary tumours and should reduce the risk of dying of this disease.
Multidrug Resistance Protein 1 Inhibitors To Sensitise Cancers To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$840,166.00
Summary
Multidrug resistance protein 1 (MRP1) is often present at high levels in cancer cells, where it pumps chemotherapy drugs back out, causing drug resistance. Inhibitors that block MRP1 would increase the effectiveness of chemotherapy. We have developed MRP1 inhibitors with promising activity in cancer cells and mouse tumours and will now develop these inhibitors for clinical application and commercialisation.
Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred bree ....Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred breeding industries contribute over $6.5 billion per annum to the Australian economy and employ thousands of staff across their value chains. However, these industries suffer from breeding program inefficiencies that amount to over $800 million in annual losses. Expected outcomes are novel reproductive technologies and specialised research capabilities that will make the Australian equine industry a global leader.Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Re-EValuating The Inhibition Of Stress Erosions (REVISE): Gastrointestinal Bleeding Prophylaxis In ICU
Funder
National Health and Medical Research Council
Funding Amount
$2,955,164.00
Summary
Around 50,000 patients in Australian Intensive Care Units receive a drug called pantoprazole each year with the aim of preventing bleeding from the gut. Recent research suggests this practice is ineffective and may harm patients by increasing their risk of serious infections. We will perform a definitive study to determine whether the widespread use of pantoprazole is beneficial or harmful.
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.
An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling w ....An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling with a novel experimental protocol to allow the study of kinetics of parasite replication in vivo. Expected outcomes will provide significant benefits, such as new avenues for vaccination and immune intervention.Read moreRead less
Development of a novel vaccine targeting parasite tegument proteins for liver fluke disease in livestock. Liver fluke parasites cause serious economic losses for livestock producers in South-East Australia, but drug resistance threatens parasite control and economic productivity in rural communities. This project will use novel technologies to identify lead vaccine candidates for improved fluke control to sustain agricultural productivity.
Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.Read moreRead less