How do interactions between axon guidance molecules bring about directed axon growth? This project deals with a fundamental, yet poorly understood biological problem at the cutting edge of international science - how axons navigate to their targets. A better understanding of this basic biological process will greatly assist the development of therapies to treat a wide range of clinical conditions in which axonal connections between neurons are disrupted by trauma or disease.
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.Read moreRead less
Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model t ....Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model to generate new knowledge of the cellular and genetic components that drive evolution of different brain parts and shapes the vertebrate brain. In doing so the project aims to provide research training, excellence and knowledge that in future may benefit health and the society. Read moreRead less
Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise ....Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise novel inhibitors of caspases. Such inhibitors may in time be used as targets for development of therapeutic or diagnostic reagents aimed at manipulating the apoptotic process to diagnose, prevent or treat disease.Read moreRead less