MOLECULAR STRUCTURE-FUNCTION RELATIONSHIPS OF THE NORADRENALINE TRANSPORTER & DRUG ACTION
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmi ....The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmitters, noradrenaline, serotonin and dopamine. Recently, the structures of the transporter proteins have been determined using molecular biology techniques. The focus of this project is to determine the parts of the noradrenaline transporter protein structure that are important in determining its functions, utilising the knowledge that we now have about its molecular structure. This will lead to exciting advances in understanding the function of the noradrenaline transporter and these advances should ultimately lead to the development of more effective antidepressant drugs and of drugs to prevent the effects of psychostimulants such as cocaine.Read moreRead less
Preclinical Investigation Into Novel Therapeutics To Treat Drug Abuse During Adolescence And Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$713,684.00
Summary
To investigate early life drug abuse and its treatment, drug-consumption and seeking behaviour will be examined in adolescent rats. We expect dopamine immaturity during adolescence to be a critical factor in persistence of drug-seeking in adolescence.
Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
Downsizing A Human Protein To Modulate Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$516,793.00
Summary
We have discovered how to downsize a human protein to very small molecules with the same activities and potencies. Small changes enable the compounds to powerfully block the actions of the protein. These small molecules are very stable in blood, whereas the protein deactivates in minutes. This project will develop the small molecules into experimental drugs and test them in human cells and proteins, and in rats to evaluate their potential for treating human inflammatory diseases.
Chronic pain is a significant global health, economic and social problem, with the annual economic burden estimated at approximately $40 billion in Australia. My research will focus on the discovery and structure-function of venom peptides (trivially called toxins) from cone snails and spiders plus other Australian venomous creatures that modulate sodium and calcium channels in peripheral pain and associated pathways and optimise these for clinical development.
Brain Pathways Underlying Vulnerability To Drug Relapse
Funder
National Health and Medical Research Council
Funding Amount
$416,788.00
Summary
Addiction to drugs is a major health and social burden for Australian society. Once addiction is established, prevention of relapse is the most significant obstacle to successful treatment. Unfortunately, efficacious pharmaceutical options to treat relapse are lacking. By employing an animal model of relapse that accurately reflects drug taking in humans the proposed project aims to advance our understanding of the brain mechanism underlying addiction.
Orexin/Hypocretin Receptors In Self-Administration And Stress-Induced Reinstatement Of Ethanol Seeking
Funder
National Health and Medical Research Council
Funding Amount
$538,221.00
Summary
Orexin receptors are novel therapeutic targets implicated in alcohol use disorders. There is little known about how orexin receptors drive ethanol consumption and stress-induced reinstatement. This project provides a unique opportunity to determine the mechanism of action of orexin receptors in alcohol use disorders and devise novel therapeutic strategies to treat alcohol use disorders.