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Hormone-dependent Autophagy And Growth Signalling In Developmental Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$613,447.00
Summary
Cell death is essential for cell and tissue homeostasis and its dysregulation is associated with many diseases. We discovered a new mode of cell death that involves autophagy. We have now identified that TGF-? signalling pathway, which has roles in numerous human pathologies, is involved in autophagy-dependent cell death. Our proposed studies will further characterise this important signalling axis and study its significance in development, normal physiology and disease.
Molecular Mechanisms Underlying Recovery From General Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$335,983.00
Summary
Even though general anaesthesia is an extremely common and safe procedure, doctors do not really know how it works. We have found that general anaesthetics might work in two steps, by first promoting natural sleep, and then by impairing communication between all nerve cells in the brain. It is this second step that makes surgery possible, but also makes recovery difficult – especially among patients with brain disorders. Understanding these mechanisms will promote better anaesthesia procedures.
Snail Family Proteins Regulate Stem Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
This research aims to discover the role of a family of genes in regulating stem cells. These genes are known to turn other genes off and we have shown that this family is required to maintain stem cells in animal tissues. The current research seeks to determine which genes are normally switched off in order to maintain normal stem cells. We also aim to determine if turning these genes on leads to cancer formation.
Regulation Of Mesenchymal To Epithelial Transitions By Netrin Receptors
Funder
National Health and Medical Research Council
Funding Amount
$646,995.00
Summary
The formation of 2D cellular sheets is important during development, tissue repair, and tumor growth. The mechanisms involved, however, remain largely unknown. Recent findings in the fly and in human cells suggest Frazzled/Neogenin receptors drive this process, by establishing polarised scaffolds in the cell. We will test this hypothesis using fly genetics and analysis of 3-dimensional culture of mammalian cells. Our results will help guide future therapies for human disease.
Genomic Investigation Of Major Human Diseases And Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
I am focused on finding disease genes for major human neurological diseases that increase with age. In my future research I will use human population genetics data combined with animal research to find genes that can block pain perception, or promote long life while preserving brain function in the elderly. My research efforts can help provide a better basic understanding of age-related diseases, and may help us identify new therapies to help us live productive, long lives.
Role Of Snail Proteins In Mediating Intestinal Stem Cell Identity
Funder
National Health and Medical Research Council
Funding Amount
$646,698.00
Summary
The lining of the intestine is constantly renewed by stem cells which also contribute to replenishment of this layer following damage caused by trauma, infection or treatments such as chemotherapy. We are studying how a family of gene regulators called Snail proteins act to maintain stem cells in the gut. Snail proteins have also been found to be present at high levels in bowel tumours so we are examining their role in the genesis of tumours and resistance to common treatments.
Defining Factors That Contribute To Individual Diversity In The Diet-health Axis
Funder
National Health and Medical Research Council
Funding Amount
$1,668,059.00
Summary
There is a complex interplay between nutrition and genetics such that one diet maybe good for some but not for others depending on genetic makeup. Preliminary experiments in flies and mice support this. We found that for some flies, diets high in fat are harmful resulting in short life but certain flies resist the harmful effects of fat and live a longer lives. We propose to unravel the gene-environment interaction and determine which genes might lead to optimal health outcomes on certain diets.
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. Because of the limited efficacy and/or safety concerns of currently available anti-obesity drugs, it is important to identify new drug targets. The results from this whole-genome scan will help to identify agents for obesity that reduce body weight and fat mass.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action