Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Do Exposures Before Conception Influence The Risk Of Asthma In Offspring?
Funder
National Health and Medical Research Council
Funding Amount
$688,586.00
Summary
Asthma and poor lung function are major causes of public health issues. Emerging evidence suggests adverse exposures even before the conception of a child may cause these conditions. The proposed project is part of an international study across generations to identify these factors. This study will provide novel evidence to guide interventions and identify studies to advance this area further. These original findings will be of great importance both nationally and internationally.
The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
The Molecular Basis For Target Selection In The Central Nervous System By Sensory Axons
Funder
National Health and Medical Research Council
Funding Amount
$251,325.00
Summary
The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct conne ....The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct connections following injury to the brain or spinal cord. We propose to use a simple model system, the embryo of the fruitfly Drosophila, to find molecules that are involved in this process of neuron target recognition - ' axon targeting' molecules - and to study how they work. Drosophila can be genetically manipulated in ways not possible in higher animals. Furthermore the simplicity of its nervous system means that we can determine the connections of individual nerve cells with a high degree of precision. In the first part of our project, we will examine Drosophila embryos that carry mutations in genes suspected to code for targeting molecules. We will stain individual sensory nerve cells in these embryos with dyes to reveal the anatomy of their axons in the brain. If sensory axons terminate abnormally in the brain of a given mutant, the affected gene is likely to code for an axon targeting molecule. In the second part of the study, we will investigate the functions of candidate axon targeting molecules using two approaches. Firstly, we will seek to determine whether the molecule acts in the sensory axons or in their target cells. Secondly, we will use time-lapse microscopy to study how the homing behaviour of the sensory axons is affected in mutant embryos. The results of these studies will lead us closer to an answer to the question: How do axons recognise their specific target cells in the brain?Read moreRead less
Congestion management in key road networks of a major city through real time data collection, intelligent forecasting and real time routing. The project researches the issues for allowing Australian Road Traffic Authorities to automatically capture road traffic data, forecast traffic flows and smartly route traffic flows to avoid congestion on road networks. This will lead to several benefits, such as (a) reducing traffic congestion, shorten travel time and lower pollution, (b) better utilizati ....Congestion management in key road networks of a major city through real time data collection, intelligent forecasting and real time routing. The project researches the issues for allowing Australian Road Traffic Authorities to automatically capture road traffic data, forecast traffic flows and smartly route traffic flows to avoid congestion on road networks. This will lead to several benefits, such as (a) reducing traffic congestion, shorten travel time and lower pollution, (b) better utilization of existing road infrastructure by diffusing traffic to alternate routes, (c) provide economic benefit by allowing one to delay infrastructure expansion, (d) monitoring of aberrant behaviour by road users to ensure a safer road environment, and (e) improved flexibility in deployment of the Wireless Sensor Network to meet the needs of the road authorities and community.Read moreRead less
Functional links between estuaries and their catchments: How does land use change affect estuarine ecological and bio-geochemical function? Estuaries are iconic recreational areas of high ecological and socio-economic value. Estuarine health is strongly linked to the catchments that feed them, yet we have no detailed understanding of these links. This project will use a number of state of the art approaches to better understand how land use affects estuarine health.
Intelligent real time multi-site controller for conserving energy in remote areas and in the resource industry. This project researches the issues in achieving demand response for electricity usage in remote regions of Australia through the use of smart meters and web of things framework to provide ubiquitous monitoring and control of devices, intelligent control systems to dynamically change energy usage patterns and community-based social network architecture. This will lead to several benefit ....Intelligent real time multi-site controller for conserving energy in remote areas and in the resource industry. This project researches the issues in achieving demand response for electricity usage in remote regions of Australia through the use of smart meters and web of things framework to provide ubiquitous monitoring and control of devices, intelligent control systems to dynamically change energy usage patterns and community-based social network architecture. This will lead to several benefits, such as (a) the strengthening of Australian business competitiveness in these regions by reducing energy costs and increasing energy trading, (b) reduction in ecological impact through smarter utilisation of energy and shifting to renewable sources, (c) encourage local generation and distribution of electricity where communities can trade excess energy.Read moreRead less
Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less