Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less
Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to p ....Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to produce the phenotype by defining the critical period and systematically identifying genes that are expressed during this period. The effect of manipulating maternal dietary omega-3 PUFA and the role of angiotensin will then be examined. The project will discover how genetic, hormonal and environmental factors interact during the perinatal period of life to program food intake and body weight in adult life. Read moreRead less
Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from natu ....Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from naturally occurring omega-3 fatty acid derivatives that are more stable to oxidation and more biologically active than fish derived omega-3 fatty acids. The development of these omega-3 derivatives as functional food ingredients could provide an additional strategy for helping to prevent the rapid increase in inflammatory mediated diseases in the Australian population.Read moreRead less
The Role Of Presenilin In Metal Homeostasis And Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$86,335.00
Summary
Presenilin, a protein involved in Alzheimer’s disease (AD), may regulate copper and zinc levels. Copper and zinc are essential nutrients however a deficiency or excess can cause disease. Promising metal-altering AD drugs, are in various stages of clinical trial. I aim to characterize the interaction of Presenilin and metals using both mouse and cultured human cell models that are deficient in Presenilin. Understanding this interaction should lead to better drug design and treatment of AD.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
What Is The Molecular Mechanism Underlying Cell Death By Necroptosis?
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Recently, we and others have demonstrated that part of the MLKL protein is able to kill cells. This process is known to cause a number of pathologies, including those arising from stroke. Blocking this type of cell death has thus emerged as an attractive therapeutic strategy. However, precisely how MLKL kills cells remains unclear and controversial. In this project, we will resolve these controversies with the goal of an increased fundamental understanding to aid drug discovery.
The Effective Treatment of Hot Dip Galvanizing Effluent Streams. Hot Dip galvanizing effluent represents a significant environmental hazard. This wastewater is currently trucked offsite and treated by contractors to precipitate a heavy metal sludge that is disposed of through landfill. Industrial Galvanisers, as the largest hot dip galvanizing company within Australia, are keen to eliminate this hazard. We will consider the use of an innovative membrane based process for this purpose; to recover ....The Effective Treatment of Hot Dip Galvanizing Effluent Streams. Hot Dip galvanizing effluent represents a significant environmental hazard. This wastewater is currently trucked offsite and treated by contractors to precipitate a heavy metal sludge that is disposed of through landfill. Industrial Galvanisers, as the largest hot dip galvanizing company within Australia, are keen to eliminate this hazard. We will consider the use of an innovative membrane based process for this purpose; to recover valuable zinc and iron compounds from the effluent and allow the water to be re-utilised. If successful, this project will lead to a pilot plant wastewater treatment plant being constructed at an Industrial Galvanizers site.Read moreRead less
The Treatment Of Galvanizing Wastewater: Delivering An Environmentally And Economically Sustainable Approach. This project will investigate a process to treat wastewater from industrial galvanizing sites around Australia. When implemented, the process will substantially reduce the consumption of acid and fresh water at these sites. Further, the process will recover the zinc content of the wastewater in a saleable form and can also generate ferric chloride for sale as a water treatment chemical. ....The Treatment Of Galvanizing Wastewater: Delivering An Environmentally And Economically Sustainable Approach. This project will investigate a process to treat wastewater from industrial galvanizing sites around Australia. When implemented, the process will substantially reduce the consumption of acid and fresh water at these sites. Further, the process will recover the zinc content of the wastewater in a saleable form and can also generate ferric chloride for sale as a water treatment chemical. The quantity of heavy metals disposed to landfill will also be dramatically reduced. Scientific knowledge of multicomponent liquid-liquid equilibria will be of value to a wider range of solvent extraction processes including zinc and copper metal refining.Read moreRead less