Characterising The Effects Of Oxidative Stress On The Human L-type Ca2+ Channel Isoforms And Role In Human Pathology
Funder
National Health and Medical Research Council
Funding Amount
$250,805.00
Summary
Oxidative stress, poor energy production and increases in intracellular calcium are features of the failing heart. I have determined that the function of the L-type calcium channel, the primary protein responsible for calcium influx and contraction can be regulated by free radicals produced by the mitochondria (powerhouse of the cell). This proposal will determine the site of modification on the human L-type calcium channel and how communication between the channel and the mitochondria is altere ....Oxidative stress, poor energy production and increases in intracellular calcium are features of the failing heart. I have determined that the function of the L-type calcium channel, the primary protein responsible for calcium influx and contraction can be regulated by free radicals produced by the mitochondria (powerhouse of the cell). This proposal will determine the site of modification on the human L-type calcium channel and how communication between the channel and the mitochondria is altered in animal models of human disease.Read moreRead less
The L-type Calcium Channel In Cardiovascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Calcium influx into cardiac muscle cells occurs via the L-type calcium channel. The channel is essential to life but when function is altered it can contribute to the development of sudden death and heart failure. I have made significant discoveries in understanding the role of the channel in disease and I have exploited this knowledge to design therapy including a novel class of calcium channel antagonists to prevent the development of heart failure.
The key goal of my research is to understand the role of protein phosphorylation in controlling metabolism, with a special emphasis on the structure and function of members of the AMP-activated protein kinase (AMPK) pathway. This is important because the function and survival of all organisms is dependent on the dynamic control of energy metabolism, with energy demand matched to energy supply.
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
Studies On The Biochemistry And Molecular Biology Of Amyloidosis
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
Amyloidoses are a group of diseases in which protein is abnormally deposited in various organs of the body. The prototypic amyloidosis is Alzheimer's disease (AD), a dementia causing-illness in which a protein known as Abeta is deposited in the brain. The central aim of my research is to understand the molecular etiology of AD and other amyloidoses, with a view to identifying new targets for drug development.