A Novel Knockin Model To Test The Role Of Nicotine Acting On Alpha4 Acetylcholine Receptors In Complex Behaviours
Funder
National Health and Medical Research Council
Funding Amount
$581,315.00
Summary
Cigarette smoking is the single largest preventable cause of death and disease in Australia and worldwide. Nicotine contained in tobacco products acts on brain nicotine receptors, which plays an intrinsic role in addiction. One type of receptor for nicotine found in regions of the brain associated with drug-seeking behaviour is called alpha4 nicotinic receptors. We have made a mouse with a mutation in this nicotine receptor to study nicotine addiction and anxiety.
Professor Lewis is a molecular pharmacologist interested in discovering new venom peptides and ciguatoxins and determining how they interact with the membrane proteins they target using advanced biochemical and spectroscopic methods. Peptides of interest are then modified to improve potency and selectivity. Those with appropriate properties are patented and developed for clinical applications using approaches successfully applied to Xen2174, a conopeptide analogue I co-discovered that is now in ....Professor Lewis is a molecular pharmacologist interested in discovering new venom peptides and ciguatoxins and determining how they interact with the membrane proteins they target using advanced biochemical and spectroscopic methods. Peptides of interest are then modified to improve potency and selectivity. Those with appropriate properties are patented and developed for clinical applications using approaches successfully applied to Xen2174, a conopeptide analogue I co-discovered that is now in Phase II clinical trials for severe pain.Read moreRead less
New Positive Allosteric Modulators Of Nicotinic Acetylcholine Receptors For Treatment Of Cognitive Impairment In ADHD
Funder
National Health and Medical Research Council
Funding Amount
$612,851.00
Summary
The effects of Attention Deficit Hyperactivity Disorder (ADHD) can extend well beyond childhood. This project will target the nicotinic acetylcholine receptor family for developing new therapeutics to manage this disease.
The Role Of Neuronal Nicotinic Receptor Subunits In The Self-Administration And Relapse To Alcohol Seeking:Treatments For Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$531,787.00
Summary
The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been sp ....The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been specifically altered by heavy alcohol intake.Read moreRead less
Computational Study Of Selectivity, Gating And Mutation In The Acetylcholine Receptor And Potassium Channels
Funder
National Health and Medical Research Council
Funding Amount
$301,393.00
Summary
One way cells in living organisms communicate with each other is via the passage of charged particles across the cell membrane. This takes place through ion channels, large protein molecules that span the membrane and allow small molecules or ions to pass through a central pore. Malfunction of ion channels is known to underlie a variety of disorders including epilepsy, hypertension, kidney disease, heart attack, deafness. Channels also provide promising targets for making new broad spectrum anti ....One way cells in living organisms communicate with each other is via the passage of charged particles across the cell membrane. This takes place through ion channels, large protein molecules that span the membrane and allow small molecules or ions to pass through a central pore. Malfunction of ion channels is known to underlie a variety of disorders including epilepsy, hypertension, kidney disease, heart attack, deafness. Channels also provide promising targets for making new broad spectrum antibiotics and antivirals. This project aims to study two important types of ion channel: acetylcholine receptors that convey signals between nerve and muscle cells, and potassium channels that regulate the nerve impulses themselves. The binding of the neurotransmitter acetylcholine released from a nerve cell to acetylcholine receptors in the muscle cell prompts the opening of a cation conductive pore. The resulting influx of ions initiates a cascade of events ending in the contraction of the muscle fibre. However, the way in which this channel opening is initiated and how ions move into the muscle cell remain to be determined. Potassium channels are primarily used to rapidly 'switch off' nerve impulses so that subsequent messages can be passed through the nerve cell. To do this they have to be highly discriminatory, allowing only potassium to pass across the cell membrane and not sodium that would initiate another impulse. Although we now know what these tiny proteins look like, it is not clear how they differentiate between types of ions while still allowing many millions to pass each second. We will use computer simulations to study how these two type of channel open and close, and how they discriminate between different ion types. Using sophisticated computational techniques on Australia's most powerful supercomputers we aim to elucidate this fundamental area of human biology in the hope of deriving treatments for some debilitating neuromuscular diseases.Read moreRead less
I am a practicing neurologist with a clinical interest in movement disorders and dementia with an international reputation in neurosciences in the fields of neural stem cells, transgenic animal models of movement disorders and epilepsy. In line with my cl