Combining PI3K, CDK4/6 Pathway Inhibitors And Immunotherapies In Triple-negative Breast Cancer (TNBC): A Novel Therapy Combination
Funder
National Health and Medical Research Council
Funding Amount
$626,345.00
Summary
Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancer subtypes, classically affecting young women and characterized by a lack of effective therapies. We show that blocking both PI3K and CDK4/6 pathways together effectively reduces TNBC growth in mice and can enhance anti-tumour immune responses. We aim to understand how these drugs work together and if adding immunotherapy can improve responses. Our project could provide a new treatment approach for TNBC patients.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Understanding The Role Of The Essential Regulator WalKR In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$555,239.00
Summary
Staphylococcus aureus is one of the most common human bacterial pathogens. This project aims to characterise an important global control system in S. aureus, and determine if chemical inhibitors of this control system could be used to treat S. aureus disease in the future.
For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
Improving Outcomes For Women Diagnosed With Mucinous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,238.00
Summary
Mucinous ovarian cancer (MOC) is different from other ovarian cancers but few studies have characterized the genetic changes specific to this subtype. It is often confused with metastases from other organs and does not respond well to standard ovarian cancer therapies. If MOC is more similar to mucinous cancers from other organs than other ovarian cancers, it may be better treated with chemotherapeutics that show success with other mucinous tumours.
Understanding and reversing the habitat shifts that have endangered the broad-headed snake. Extinction rates for vertebrate species are higher in southern Australia than almost anywhere else in the world, and saving endangered taxa is critical to biodiversity conservation. To do this effectively, researchers need to understand the processes that threaten wild populations, and to develop novel solutions to those problems in close collaboration with wildlife management authorities and other stake ....Understanding and reversing the habitat shifts that have endangered the broad-headed snake. Extinction rates for vertebrate species are higher in southern Australia than almost anywhere else in the world, and saving endangered taxa is critical to biodiversity conservation. To do this effectively, researchers need to understand the processes that threaten wild populations, and to develop novel solutions to those problems in close collaboration with wildlife management authorities and other stakeholders. This project will build such an understanding and collaboration, focusing on an endangered snake species. We propose ambitious landscape-scale field experiments that will simultaneously test hypotheses on threatening processes, and restore habitat quality to reverse population declines.Read moreRead less
Is recruitment of marine invertebrates affected by variation in larval quality? Managing marine populations and habitats requires detailed understanding of how populations are replenished, and why some places receive more new recruits than others. Attempts to reach this understanding have been hindered by the difficulty in studying tiny larvae that live in the plankton, and for most species, recruitment is a highly variable, unexplained phenomenon. We have identified a new explanation for this ....Is recruitment of marine invertebrates affected by variation in larval quality? Managing marine populations and habitats requires detailed understanding of how populations are replenished, and why some places receive more new recruits than others. Attempts to reach this understanding have been hindered by the difficulty in studying tiny larvae that live in the plankton, and for most species, recruitment is a highly variable, unexplained phenomenon. We have identified a new explanation for this variation, and will test this explanation using a marine invertebrate that is one of Australia's marine pests. A positive result offers promise of explaining recruitment variation in other species, and will provide insight into what makes this particular pest species successful.Read moreRead less
Do costs of dispersal reduce connectivity in marine invertebrate populations? Current approaches to marine management - designing marine reserves, understanding pest incursions, and managing fisheries, acknowledge that marine animals exist in isolated local populations, connected by dispersal. Dispersal is crucial for local populations to persist or be managed sustainably, but our understanding remains poor and often limits our management. Most current approaches to estimating connectivity are ....Do costs of dispersal reduce connectivity in marine invertebrate populations? Current approaches to marine management - designing marine reserves, understanding pest incursions, and managing fisheries, acknowledge that marine animals exist in isolated local populations, connected by dispersal. Dispersal is crucial for local populations to persist or be managed sustainably, but our understanding remains poor and often limits our management. Most current approaches to estimating connectivity are adequate only if all dispersers are equally successful at establishing. Dispersal, however, is risky or costly, and we propose that these costs reduce the success of colonists from more distant populations. If this is correct, persistence of local populations may rely disproportionately on other nearby local populations.Read moreRead less
Capture stress and post-capture survival of sharks and other chondrichthyans in fisheries bycatch. Australia is adopting ecosystem approaches to fisheries management. However, to embrace such an approach there is an urgent need for better information on the biology, ecology and population dynamics of sharks, rays and chimaeras (class Chondrichthyes). Chondrichthyan species are among the most sensitive in their response to the effects of fishing. Results from the present proposal will contribute ....Capture stress and post-capture survival of sharks and other chondrichthyans in fisheries bycatch. Australia is adopting ecosystem approaches to fisheries management. However, to embrace such an approach there is an urgent need for better information on the biology, ecology and population dynamics of sharks, rays and chimaeras (class Chondrichthyes). Chondrichthyan species are among the most sensitive in their response to the effects of fishing. Results from the present proposal will contribute to determining mortality of chondrichthyan bycatch species in response to the effects of capture in fishing gear, handling by fishers and discarding at sea. The work will contribute to biodiversity conservation and maintenance of ecosystem structure and function for present and future generations.Read moreRead less