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.
GTPase Regulation Of The Hippo Organ Size-control Pathway
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which two proteins, Pix and Git, control tissue growth by regulating the Hippo pathway. These studies will be performed in flies. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
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.
Role Of Snail Family Proteins In Male Fertility And Testicular Cancer
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Male fertility requires production of healthy sperm in the testis. This project builds on our discoveries that testicular cells regulate gene activity via the Snail family of proteins during sperm development, and that interruption of their activities reduces fertility in mice and fruitflies. Snail proteins are also active in cancer cells. We propose to study the precise steps in sperm production affected by Snail proteins and how they affect the progression of testicular cancer.
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.
Autophagy And Growth Signalling In Developmentally Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$594,133.00
Summary
Cell death is essential for normal development and deregulated cell death results in many diseases. We have recently discovered a potentially novel mechanism of developmental cell death that involves autophagy (a type of self-degradation). Our studies will now examine the mechanism of autophagic cell death and study how cell growth regulation is integrated in this pathway. This will provide us important knowledge into the complex role of autophagy in cancer.
Stem cell to differentiation occurs in a bi-directional fashion. Dedifferentiation which allows specialized cells to become stem cells has been found to be important in both cancer and regeneration. In this proposal, we will investigate the metabolic reprogramming of neuronal dedifferentiation. The findings from this study will better inform us on how to specifically target tumours that arise from dedifferentiation.
Wbp2, A New Regulator Of The Hippo Tumor Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which a newly-identified Hippo pathway protein, Wbp2, functions to control growth. These studies will be performed in flies and confirmed in mammalian cells. Ultimately, our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
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.