Developing Novel Agents To Prevent Tumour Recurrence In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$1,089,561.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called KDM4 (using 'KDM4 inhibitors') improves chemotherapy outcomes with new drugs also discovered in our laboratory. This project will examine a novel drug combination treatment for glioblastoma patients and generate evidence for initiation of clinical trials. This could initiate a novel therapy that could significantly extend patients' lives.
Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.
Development Of Novel Anti-malaria Drugs That Block Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$1,035,623.00
Summary
Malaria is a devastating parasitic disease that kills over 400,000 people a year. Antimalarial drugs play a crucial role in helping eradicate malaria but of great concern is that parasites are becoming resistant to current drugs. We are developing drugs that prevent parasites from invading and proliferating in human blood which causes malaria. We are also discovering how the drugs work with the aim of greatly improving their performance towards clinical uptake.
Molecular Characterisation Of The DBHS Proteins In Telomerase Assembly
Funder
National Health and Medical Research Council
Funding Amount
$686,246.00
Summary
Telomerase is an enzyme that is active in over 90% of cancers. Telomerase activity allows cancer cells to divide an indefinite number of times. We have identified a novel role for the DBHS protein family in regulating telomerase activity. We aim to investigate the mechanisms by which these proteins function to assemble and transport telomerase to its site of action in the cell. We then aim to develop chemical inhibitors of these proteins, and test their utility in preventing cancer cell growth.
New Therapeutic Approaches For Genetic Skeletal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$961,150.00
Summary
Genetic skeletal disorders are a significant disease burden with limited therapeutic options. We will use mouse models of cartilage and bone disorders and human induced pluripotent stem cell derived bone and cartilage 'disease in a dish' models to test repurposed FDA-approved drugs and new drug candidates as novel therapeutic strategies.
Validating CaMKK2 As A Rational Treatment Target For Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$688,175.00
Summary
Bipolar disorder is a disabling, chronic mental illness that profoundly impairs the ability of affected individuals to function in daily life. Existing treatments for bipolar disorder are inadequate and lack the necessary efficacy and tolerability required for long-term therapy. This project will validate the enzyme, CaMKK2, as a rational treatment target for bipolar disorder, which will guide the development of more effective and safer drugs to improve patient outcomes.
Repurposing And Re-optimising Drugs That Disrupt Glycoprotein Folding To Treat COVID-19
Funder
National Health and Medical Research Council
Funding Amount
$1,199,874.00
Summary
As of June 2020, COVID-19 has infected over 7.3 million people and killed over 413,000 in the six months since it emerged. It has pushed many healthcare systems and economies to breaking point. We recently discovered that a known drug is effective at stopping the virus under laboratory conditions. This research will determine exactly how the drug works, evaluate it's potential in pre-clinical models, and re-optimise the drug's antiviral properties to ensure that we can prevent future pandemics.
Spinosyns As Endectocides For Blocking Transmission Of Malaria And Other Mosquito-borne Diseases
Funder
National Health and Medical Research Council
Funding Amount
$758,299.00
Summary
Malaria is a disease caused by a parasite. It is transmitted by mosquitoes and kills 400,000 people annually. To prevent malaria we must stop transmission. We have discovered a natural substance that, if ingested, makes an animal's blood lethal to at least one type of mosquito. It also kills the parasite. We aim to determine if it kills other key mosquito types and how it kills the parasite. We expect this study will lead to a pill that stops transmission of malaria and other tropical diseases.
The blood-brain barrier is a major impediment to the treatment of brain tumours because it prevents most anti-cancer drugs from entering the brain, and brain tumour, from the bloodstream. This proposal examines new approaches to open the blood-brain barrier to allow the use of existing highly potent anti-cancer drugs as brain cancer therapies. Successful outcomes of this work could lead to substantial improvements in the outcomes for brain tumour patients.
Identification Of Therapy-resistant Cells Driving Relapse In Medulloblastoma From Integrated Spatial Transcriptomics And Tissue Imaging
Funder
National Health and Medical Research Council
Funding Amount
$749,272.00
Summary
Medulloblastoma (MB) is the most common cause of cancer related mortality in children, with relapsed MB nearly a universally fatal event. Relapsed MB can be caused by pre-existing rare cells that escape treatment and continue to evolve. This project will identify the organisation of all cell types within patient derived xenograft models of MB, monitoring how this changes throughout tumour progression and drug treatment. We will identify rare cells responsible for driving recurrence.