The Bcl-2 family of proteins is crucial for apoptosis (a form of programmed cell death) regulation. They target the mitochondrial outer membrane where they interact to determine cell fate. We will evaluate the membrane interactions of the Bcl-2 proteins in complementary biophysical and cellular experiments to redefine our understanding of the mechanism of apoptosis and provide new avenues for the development of compounds to selectively modulate diseases in which apoptosis is unregulated.
Targeting Dysfunctional Mitochondria In Macrophages To Inhibit Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$1,009,796.00
Summary
The major contributing cells to heart disease are macrophages. These cells scavenge cholesterol, keeping the blood vessels clean and limiting heart disease. The macrophages must process and donate the scavenged cholesterol onto HDL-cholesterol that carries them back to the liver for removal. This process requires the powerhouse of the cell, the mitochondria to be functional. We have discovered that process fails and have novel drugs to re-instate this process of cholesterol removal.
Mitochondrial Quality Control In Parkinson’s Disease: The Molecular Mechanisms Of PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$558,721.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two genes that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
Carnitine Acetyltransferase (CrAT) Regulates Appetite And Body Weight Through The Melanocortin System
Funder
National Health and Medical Research Council
Funding Amount
$547,087.00
Summary
Carnitine metabolism in peripheral tissues, such as muscle, maintains appropriate cellular metabolism and function. Little is known about carnitine metabolism in specific populations of brain cells regulate food intake and appetite. This project aims to understand how carnitine metabolism affect brain cells that regulate food intake and body weight.
Defining The Machinery For Mitochondrial Turnover Governed By The Parkinson’s Disease Proteins PINK1 And Parkin
Funder
National Health and Medical Research Council
Funding Amount
$432,987.00
Summary
Parkinson’s disease is a degenerative disorder of the central nervous system in which the underlying cause is mostly unknown. To pave the way to a better understanding of what goes wrong, this study will investigate the function of PINK1 and Parkin, two proteins that are mutated in inherited forms of the disease that play important roles in maintaining cellular health. The results of this study will be used in exploring new therapeutic targets for the treatment of Parkinson’s disease symptoms.
Boosting Mitochondria- A New Approach For Protecting The Aging Optic Nerve In Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$391,784.00
Summary
Increasing age is a major risk factor for neurodegeneration. We have recently shown that subjecting mice to intermittent periods of fasting improves mitochondrial function in the retina and reverses age-related decline in optic nerve vulnerability to injury. This project now aims to investigate key molecular pathway for restoring mitochondria and from this attempts to find more palatable therapeutic strategies for protecting the optic nerve from injury.
Carnitine Palmitoyl Transferase 1 In POMC Neurons Controls Glucose Homeostasis And Body Weight
Funder
National Health and Medical Research Council
Funding Amount
$474,499.00
Summary
The brain plays a critical role in body weight gain by balancing appetite-inducing and appetite-suppressing signals. An imbalance in this process causes obesity, promotes diabetes and cardiovascular disease. The aim of this research is to identify how appetite-suppressing brain signals are maintained as a method to prevent obesity progression.
Systems Approaches To Understanding The Assembly Of Mitochondrial Machines
Funder
National Health and Medical Research Council
Funding Amount
$600,005.00
Summary
Mitochondria produce the energy for our bodies. Defects in this process cause mitochondrial disease, which affects at least 1/5000 people. Diagnosis is often inconclusive as we do not understand the function of many proteins important in mitochondrial energy production. State of the art CRISPR gene-editing tools will be coupled with advanced proteomics techniques to model different types of mitochondrial disease and identify the functions of new candidate disease genes.
An Investigation Into Pathogen-specific Factors Required For Drug-resistance And Viability Of Candida Albicans
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
We identified proteins required for growth and drug resistance of the fungus Candida albicans, a major hospital-acquired human pathogen. Candida infections target the immunocompromised and mortality is huge (?30-50%). We will use cell biology, genetics and biochemistry to characterise these proteins. Importantly, these factors are present in fungi, but absent from humans. Therefore our study will help development of new strategies for antifungal treatments.
How Does Exercise Ameliorate Programming Of Metabolic Dysfunction In Offspring Of Obese Mothers?
Funder
National Health and Medical Research Council
Funding Amount
$524,121.00
Summary
Obesity is a worldwide disease, reflecting an interaction between our environment (diet, physical activity) and genes. We know that a mother's unhealthy diet can predispose offspring to diabetes, and exercise can improve this, but the underlying mechanisms are poorly understood. Here we will examine how exercise can benefit offspring of obese mothers, and test a drug that mimics the effects of exercise. The proposed research will provide insight into ways of reducing the obesity epidemic.