Development Of A New High Throughput Screen For Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$351,320.00
Summary
Inadvertent drug block of hERG, a potassium channel in the heart, can cause cardiac arrhythmias and sudden cardiac death. Screening for hERG toxicity has become a major hurdle for development of new drugs. We will use a mutant hERG protein that has enhanced drug binding to develop a high throughput test for hERG toxicity. Identification of dangerous drugs early in the drug discovery process will save the pharmaceutical industry millions of dollars in the costs of brining new drugs to market.
Drug Resistance In DNA Repair Defective Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$122,032.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and respond to new PARP inhibitor therapy, yet even then the cancer often recurs. I will use a new model to study human ovarian cancers in mice. My focus will be understanding resistance to PARP inhibitors in individual ovarian cancers and designing approaches to overcome this resistance.
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.
TARGETING A NOVEL DNA-DAMAGE SIGNALING PATHWAY TO TREAT GLIOMAS
Funder
National Health and Medical Research Council
Funding Amount
$97,783.00
Summary
Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to ....Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to their upregulation in tumour cells.Read moreRead less
Structure-based Drug Design For Neuroprotection From Traditional Chinese Medicine
Funder
National Health and Medical Research Council
Funding Amount
$245,968.00
Summary
In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative di ....In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative disease.Read moreRead less
Glucocorticoid Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$394,721.00
Summary
Glucocorticoids are among the most effective drugs used in the treatment of many haematological malignancies, including leukaemia, lymphoma and multiple myeloma. However, the development of tumour cell resistance to these drugs remains a significant problem, and clinically relevant mechanisms of glucocorticoid resistance remain poorly understood. This project aims to define mechanisms of resistance to glucocorticoids and develop new drugs to reverse resistance.
A Zebrafish Model Of Facioscapulohumeral Dystrophy For Therapy Development And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$390,601.00
Summary
This project seeks to develop a zebrafish model for a genetic muscle-wasting disease called facioscapulohumeral dystrophy (FSHD). Our zebrafish model will enable us to better understand the biological mechanisms underlying the disease, as well as provide a platform for therapeutic testing and discovery.
Improved Risk Assessment For Drugs Causing Cardiac Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$638,166.00
Summary
Fatal heart rhythm disturbances are an all too common side effect of many drugs. Tests that are in place to guard against this are effective, but widely considered too stringent, meaning the development of potentially useful new therapeutics has been hampered. This study will characterise the precise mechanisms by which drugs cause arrhythmias and identify specific patterns on patient ECGs associated with the risk of rhythm disturbances that can be used in more effective clinical testing.
Novel Inhibition Of Cancer Cell Growth In Gastrointestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$47,474.00
Summary
This research project will focus on new treatment targets for gastrointestinal malignancies, focusing on the mTOR pathway which is important in driving cancer cell growth. The mTOR inhibitor drug Everolimus will be used in colon and biliary tract cancers to look for novel biomarkers of response and resistance to treatment, using cancer cell lines and correlative analysis with data obtained from patients' tumour samples and clinical assessment in current trials.
Design, Development And Analysis Of New Tuberculosis Drugs
Funder
National Health and Medical Research Council
Funding Amount
$736,628.00
Summary
Serious issues of drug resistance have emerged in tuberculosis prevention and are placing enormous pressure on global health systems. We have identified an enzyme of M. tuberculosis that is essential for its survival. This project will develop potent inhibitory compounds for this enzyme. Further, we will identify new drug targets through a screen to specifically identify the genes of the organism essential for its survival in the body. This information will be used to develop new TB drugs.