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Pharmacological Targeting Via AKT, PTEN, And TGF-beta Pathway Integration Using Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$634,875.00
Summary
We have identified potentially important interactions of cellular pathways that vary between individual sufferers, but which also provide common molecular targets for novel drug development. Our suite of novel and potent drugs that markedly and selectively inhibit cancer cell growth will be studied to determine if these pharmaceutical agents act to inhibit tumour cell proliferation by targeting common effector molecules of integrated cellular pathways.
Pre-clinical Development Of A Novel Second Generation Chemotherapeutic For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$584,907.00
Summary
Cancer cells have a high iron requirement for DNA synthesis and many clinical trials have shown that iron chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of the iron chelator, Triapine, into widespread NCI clinical trials. In this NHMRC Development Grant, we will perform toxicological studies to enable clinical trials of our most potent and selective anti-cancer agent to commence.
Irritable Bowel Syndrome (IBS) is one of the leading causes of chronic pain both world-wide and in Australia for which there is a lack of treatments. Chronic pain arises from nerve fibres in the colon wall, which fail to 'reset' back to normal following inflammation. Targeting these nerve endings with drugs is a key advance in IBS treatment. This project will identify selective oxytocin analogues that act in the colon to lower pain in sensory nerves thus providing efficacious pain relief in IBS.
Novel Analogues Of Human INSL3 As Antagonists And Probes Of Testicular Function
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
The hormone, insulin-like peptide 3, has recently been shown to act directly on male and female germ cells to cause their maturation. It has considerable promise as a therapeutic agent for the regulation of fertility. Drugs based on the peptide may be used to assist in cases of infertility, and drugs that block its action have great potential as male and female contraceptives. Towards these goals, our project aims to understand how this peptide exerts its unique biological effects.
The Structural Basis For Promiscuity Of Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$713,035.00
Summary
Special proteins called ion channels control the electrical activity of the heart. Drugs that block ion channels can have the unwanted side-effect of altering the rhythm of the heart beat and causing sudden cardiac death. Extensive efforts are made to screen for this problem during drug development but it is still an inexact science. Here we will use high resolution imaging technologies to get a better understanding of how drugs bind to ion channel proteins.
The Mechanisms Responsible For Tolerance At The Mu-opioid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Strong pain relieving opioid drugs like morphine lose their effectiveness when used for long periods because the single protein target for them in the body loses its� normal signalling functions. This research will determine the mechanisms responsible for this loss of function in brain nerve cells using novel methods to identify the molecular adaptations involved. This will provide a rational framework for development of pain relieving opioid drugs that can maintain long term efficacy.
Cellular Response To Modulation Of Iron Levels: Studies Examining ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$33,055.00
Summary
Iron is crucial for many essential biological processes. Recently, I demonstrated that iron-depletion can affects signalling pathways that play important roles in cellular growth and death. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. My proposed research is crucial for understanding: (1) the effects of iron-deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.
Positive Allosteric Modulation Of Metabotropic Glutamate Receptor 5; A Novel Approach For The Treatment Of Schizophrenia And Cognitive Disorders
Funder
National Health and Medical Research Council
Funding Amount
$348,428.00
Summary
The metabotropic glutamate receptor subtype 5 (mGluR5) has emerged as an exciting new target for the treatment of schizophrenia and cognitive disorders. We will investigate novel drug-binding sites on these receptors with the aim to discover new therapeutics. These studies also aim to definitively characterize mGluR5 activity following treatment with novel compounds to improve our understanding of the normal function of these important receptors.
Defining The Mechanisms Of Action For Ozonide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$668,152.00
Summary
Deadly malaria parasites have emerged that are resistant to all classes of approved drugs. Ozonides are a new class of medicines recently approved for malaria, and provide a much-needed treatment option for multi-drug resistant infections. However, the mode of action and potential for cross-resistance is poorly understood. This project will use modern analytical techniques to measure the impact of ozonides on parasite biochemistry to reveal mechanisms involved in drug action and resistance.
UGT Enzymes In Chemotherapeutic Drug Metabolism: New Avenues To Improve Drug Response And Overcome Resistance
Funder
National Health and Medical Research Council
Funding Amount
$610,005.00
Summary
Tumours treated by chemotherapy often become resistant to the drugs, leading to relapse and reduced chance of survival. We will study one of the main pathways leading to drug resistance, which could lead to the development of new ways to overcome resistance and improve cancer treatment outcomes.