Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
The Role Of Accessory Subunits And Assembly Factors In The Biogenesis Of Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$569,987.00
Summary
The mitochondrial respiratory chain produces most of the energy required for our cells to grow and function. Complex I is the first enzyme of this chain and its defects are the most prevalent cause of mitochondrial disease, which often results in infant fatality. Defects in complex I have also been associated with Parkinson's disease and oxidative stress. This study will provide important new information into how complex I is built and what goes wrong to cause disease.
Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Viewing The Cellular Responses In Huntington’s Disease Through An Aggreomics Framework
Funder
National Health and Medical Research Council
Funding Amount
$363,218.00
Summary
Huntington disease results from a mutation that causes the Htt protein to form abnormal toxic clusters in neurons that eventually leads to cell death. This project will develop and apply new technology to identify how the clustering process damages cells and will measure all the gene expression changes that occur during the clustering process. The project offers much potential for revealing new therapeutic targets to this incurable disease.
AMPK Control Of Lipid Metabolism: Role In Regulating Energy Balance And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$614,437.00
Summary
The control of appetite and maintenance of a lean body mass along with exercise is important for protecting the body against obesity and increased incidence of Type 2 diabetes and cardiovascular disease. We are investigating how the regulation of lipid metabolism controls appetite and body weight and the extent to which these same controls are important for drugs acting to lower blood lipid levels.
Inhibition Of AMPK Signalling As A Strategy For Decreasing Appetite
Funder
National Health and Medical Research Council
Funding Amount
$644,266.00
Summary
The enzyme AMP-activated protein kinase (AMPK) has previously been implicated in mediating increased food intake in response to fasting and the appetite-inducing hormone ghrelin. In this study we propose to investigate whether inhibition of AMPK has promise as a strategy to reduce hunger in the context of dietary restriction and increases in energy expenditure, such as exercise. We will also test whether a new AMPK inhibitor has the potential to reduce appetite signalling in cells and in mice.
Mammalian cells have developed a complex signalling network responsible for monitoring and responding to changes in the levels of growth factors and the availability of nutrients, energy and oxygen in their environment. Deregulation of this network often results in uncontrolled cell growth and diseases including cardiac hypertrophy and cancer. This proposal aims to understand how this network controls cell growth and identify potential targets for diseases driven by uncontrolled growth.
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.