Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
Molecular Regulation Of Apoptosis In Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
This project seeks to understand the mechanisms by which cells that make up our blood vessels are kept alive. Impaired blood vessel cell survival contributes to reduced blood vessel health, a major component of cardiovascular disease. Knowledge of how these cells are kept alive could prove useful in treating diseases affecting vessel cell survival, or potentially to combat those diseases that are caused by excessive blood vessel growth.
Analysis Of Rho GTPase Signalling Pathways In An Epithelial To Mesenchymal Transition During Development Of The Mesoderm
Funder
National Health and Medical Research Council
Funding Amount
$409,500.00
Summary
A critical step in the progression of cancers that are derived from epithelial tissues is a transition from an epithelial cell type to a migratory mesenchymal cell type that can spread to other parts of the body. This change in cell behaviour also occurs, apparently by a similar mechanism, during the development of some normal tissue types. Here we propose to use an animal model of this process, coupled with advanced molecular genetic and cell biological techniques, to investigate a newly discov ....A critical step in the progression of cancers that are derived from epithelial tissues is a transition from an epithelial cell type to a migratory mesenchymal cell type that can spread to other parts of the body. This change in cell behaviour also occurs, apparently by a similar mechanism, during the development of some normal tissue types. Here we propose to use an animal model of this process, coupled with advanced molecular genetic and cell biological techniques, to investigate a newly discovered cell signalling mechanism required for the transition of cells from an epithelial form to a mesenchymal form. Understanding the molecular steps in this new pathway and discovering new genes involved will provide tools for understanding and preventing the metastasis of cancer cells.Read moreRead less
The Role Of Raptor And Rictor Signalling Pathways In Osteogenesis And Mesenchymal Stem Cell Fate Determination
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Skeletal diseases associated with excessive bone loss and skeletal fragility, such as osteoporosis, affect 2.2 million Australians and cost our health system approximately $7.4 billion per annum. Studies from our laboratory suggest a critical role for the mTOR signalling pathway in bone development. Using transgenic animals and state-of-the-art techniques, we will investigate the role of mTOR in pre- and post-natal skeletal development. Results from these studies may provide novel approaches to ....Skeletal diseases associated with excessive bone loss and skeletal fragility, such as osteoporosis, affect 2.2 million Australians and cost our health system approximately $7.4 billion per annum. Studies from our laboratory suggest a critical role for the mTOR signalling pathway in bone development. Using transgenic animals and state-of-the-art techniques, we will investigate the role of mTOR in pre- and post-natal skeletal development. Results from these studies may provide novel approaches to treat age-related bone loss syndromes.Read moreRead less
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.
Mechanisms Of Muscle Stem Cell Action In Injury And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$812,600.00
Summary
How do stem cells work in an organ or tissue to effect repair? Skeletal muscle is one of the few tissues that possesses the ability to regenerate after injury or disease but we understand very little about the processes that govern stem cell activation and the biology of self renewal, the mysterious process by which stem cell populations replicate themselves. Our zebrafish system will allow us to examine these questions directly in living muscle.
Revealing How The Mammalian Preimplantation Embryo Undergoes Compaction
Funder
National Health and Medical Research Council
Funding Amount
$705,102.00
Summary
The first morphological process critical for mammalian development is embryo compaction. During compaction, cells change their morphology from rounded to wedge-like. The mechanisms controlling embryo compaction remain unclear. We recently discovered that during compaction, cells extend long membrane protrusions on top of each other. In this Project we will establish the role of these protrusion in controlling embryo compaction and reveal the mechanisms underlying their formation.
Revealing How Transcription Factors Search The DNA To Control Preimplantation Development In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
The development of mammalian embryos relies on proteins that bind to DNA to activate different genes. While several proteins regulating genes during embryonic development have been identified, it remains unknown how these proteins find their specific DNA targets. We will apply new non-invasive methods to analyse the movement of DNA–binding proteins in intact mouse embryos undergoing normal development, and will determine the molecular mechanisms that control DNA–protein interactions.
DECIPHERING THE ROLE OF FOXP1 IN MAMMARY STEM CELLS AND DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$569,109.00
Summary
Breast (mammary) epithelial cells undergo major changes across developmental stages, including puberty, pregnancy and lactation. This project will focus on the role of the molecular regulator, Foxp1, and how it influences normal mammary maturation. This work will inform whether Foxp1 is critical for controlling the activation of dormant stem cells and if this pathway can contribute to breast cancer formation when disrupted.
Elucidating The Tumour Suppressor Behaviour Of FUBP1 In Glioma
Funder
National Health and Medical Research Council
Funding Amount
$940,780.00
Summary
Treatment strategies for patients with invasive brain tumours are based on a WHO tumour grading system. This system does not account for differences within tumour types, although these can significantly affect treatment outcomes. This project aims to investigate new drug therapies for specific brain tumour types, and to identify new prognostic markers for these tumours. These studies will lead to more individualised treatments, which is critical to improving patient survival and quality of life.