Cellular Mechanisms Controlling Neural Crest Cell Migration Along The Developing Gut
Funder
National Health and Medical Research Council
Funding Amount
$368,895.00
Summary
Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by ne ....Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by neuron precursors takes 5 days in mice and 6 weeks in humans. Studies of the mechanisms controlling the migration of neuron precursors along the gut have provided fundamental information about cell migration in general. Genetic studies in humans and mice have identified some of the genes that are necessary for the migration of neuron precursors along the gastrointestinal tract, but for some of the key genes, their precise role is unknown. We have recently developed a method for imaging living neuron precursors migrating through explants of embryonic mouse gut. In the current proposal we will meld imaging and genetic studies to understand how mutations in particular genes lead to migration defects. In particular, how do particular mutations affect the migratory behaviour of enteric neural precursors? We have also previously shown that neuron precursors migrate along the gut in close association with axons. We will examine the nature of these interactions - in particular, who is following whom, and what happens when cell migration and axon growth are uncoupled? These studies, which will investigate a number of critical aspects of the migration of neural precursors into and along the developing gut, are central to understanding how the enteric nervous system is established along the gastrointestinal tract.Read moreRead less
A Novel Treatment For Ischemic Stroke: Preclinical Assessment In The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$762,246.00
Summary
A major source of repair inhibition after brain injury is debris from dying cells, which contains proteins that hinder repair. This project will examine the expression of these proteins in a clinically-relevant model of ischemic stroke and determine if blocking the effect of these proteins neutralises their repair-inhibiting properties. If successful, there is likelihood that this drug, and method of delivery, could be translated into the human for treatment following an ischemic stroke.
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.
Fluid security in the Asia Pacific. At a time of global and regional insecurity fuelled by economic and terrorism concerns, this project will provide a rigorous evidence base for the Asia Pacific to better manage mobility in a more inclusive way. This directly fits with understanding our region and the world by providing an evidence base for better understanding of how and why people move throughout the Asia Pacific and their impact and experiences of security. It also contributes to protecting ....Fluid security in the Asia Pacific. At a time of global and regional insecurity fuelled by economic and terrorism concerns, this project will provide a rigorous evidence base for the Asia Pacific to better manage mobility in a more inclusive way. This directly fits with understanding our region and the world by providing an evidence base for better understanding of how and why people move throughout the Asia Pacific and their impact and experiences of security. It also contributes to protecting Australia from terrorism and crime by identifying the reasons and ways people move in unauthorized ways and therefore to help to design systems that reduce experiences of victimization and criminalisation.Read moreRead less
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
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
The Role Of Rnd Genes During Cortical Neurogenesis And Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$410,384.00
Summary
In order for the brain to function properly, tens of billions of neurons within it first have to be born, then find their proper location before connecting with other neurons in a highly ordered fashion. Failure of these key processes heavily impacts on subsequent brain function, and have been shown to underlie several disorders including epilepsy. This study will investigate how members of the Rnd gene family control cell production and positioning within the developing brain.
Understanding the Factors which Underlie Successful Refugee Integration in the Australian Workplace. There is general agreement that more needs to be done to integrate refugees into the Australian workplace. This project aims to: identify psychological predictors that enable refugee workers to succeed in maintaining their employment and perform at a higher level; examine the importance of workplace and social support to refugee workplace integration, and the groups for which it may have the grea ....Understanding the Factors which Underlie Successful Refugee Integration in the Australian Workplace. There is general agreement that more needs to be done to integrate refugees into the Australian workplace. This project aims to: identify psychological predictors that enable refugee workers to succeed in maintaining their employment and perform at a higher level; examine the importance of workplace and social support to refugee workplace integration, and the groups for which it may have the greatest benefit; and, investigate the effectiveness of a training program as an intervention to enhance refugee job performance and retention. Results will have significant benefits for refugees, their employers and their communities, and will provide a road-map to improve integration of refugees into Australian society.Read moreRead less
Pacific Labour and Australian Horticulture. This 18-month research project will investigate the costs and benefits of increasing labour mobility between the Pacific and Australia, including the feasibility of a seasonal labour program to employ agricultural workers from Pacific Island nations in the Swan Hill/Mildura region during periods of peak labour demand. It will forge a ground-breaking collaboration between an international development agency and local government to investigate how such a ....Pacific Labour and Australian Horticulture. This 18-month research project will investigate the costs and benefits of increasing labour mobility between the Pacific and Australia, including the feasibility of a seasonal labour program to employ agricultural workers from Pacific Island nations in the Swan Hill/Mildura region during periods of peak labour demand. It will forge a ground-breaking collaboration between an international development agency and local government to investigate how such a scheme might contribute simultaneously to economic and social development in Pacific Island nations (through remittances and skills transfers) and in regional Australia (by improving the labour supply to key horticultural industries).Read moreRead less
Visual Anthropology of settlement among newly arrived refugee youth. The majority of refugees currently arriving in Australia are youth from the middle-East and the Horn of Africa. These young people face major challenges to successful settlement, often having histories of little or no schooling, exposure to violence, and long-term residence in refugee camps. There is a lack of evidence to inform policy and practice on how to best support these young people. This project will give refugee youth ....Visual Anthropology of settlement among newly arrived refugee youth. The majority of refugees currently arriving in Australia are youth from the middle-East and the Horn of Africa. These young people face major challenges to successful settlement, often having histories of little or no schooling, exposure to violence, and long-term residence in refugee camps. There is a lack of evidence to inform policy and practice on how to best support these young people. This project will give refugee youth the opportunity to learn technical, creative and interpersonal skills, enabling them to share their stories with both researchers and the general public and producing understandings about how they cope with the resettlement process. Read moreRead less