Osteocytes, the most abundant and long-lived, yet least studied bone cell, are increasingly recognised as key controllers of bone remodelling and are implicated in many bone diseases. Our work is uncovering novel molecular and cellular pathways by which osteocytes act and survive in bone, which is generally an oxygen-deprived tissue. This will provide a rational basis to seek improved treatments of bone disease.
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.
NDI1 Therapy For NADH-Ubiquinone Oxidoreductase Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$575,762.00
Summary
This study will test a new protein therapy that can act as a surrogate for a deficient or defective enzyme called Mitochondrial Complex 1. The deficiency occurs in newborns with defective genes for the proteins that form the enzyme. The defect causes metabolic malfunction in most organs, with patients needing specialist hospital and parental care, but there is no cure yet. We have successfully tested this in the lab but will now test this in our new animal model of the disease.
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.
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.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.