Discovering Molecules And Mechanisms Regulating Dendrite Formation
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
Dendrites are neuronal projections necessary to receive stimuli from other neurons or the external environment. Abnormalities in dendrite development associate with mental retardation and other human conditions such as Down syndrome, Rett syndrome and Fragile-X syndrome. The studies presented in this proposal, using the powerful genetic and molecular tools available for the nematode C. elegans, will provide new insight into the cellular and molecular mechanisms regulating dendrite development.
THE ROLE OF UBIQUITIN LIGASE ADAPTOR PROTEIN NDFIP1 IN NEURONAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$581,813.00
Summary
Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UP ....Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UPS.Read moreRead less
Molecules and mechanisms regulating axonal degeneration and regeneration in Caenorhabditis elegans neurons. Understanding the molecular mechanisms underlying nerve degeneration and regeneration is essential to tackle and provide treatment for neurodegenerative diseases and injury of the nervous system. This project aims to discover, using a genetic approach and a simple animal model system, the molecules regulating these crucial biological processes.
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.
DCC-Robo Interactions Cooperate To Regulate Callosal Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$383,422.00
Summary
In order for the brain to function, the correct connections between neurons must be formed during development. These connections, formed by the axonal processes of neurons, are able to find their synaptic targets by sensing molecular cues within the brain that guide them, by attraction or repulsion, to their target. This proposal investigates how attractive and repulsive signals are received and integrated in neurons to enable axons to find their targets in the brain.
The Role Of Central And Peripheral Synaptic Activity In The Developmental Death Of Motoneurons.
Funder
National Health and Medical Research Council
Funding Amount
$463,145.00
Summary
Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on ....Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well characterised part of the nervous system. During development, 50% of motoneurons die at a time when they are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal connections that ultimately result in neuronal death.Read moreRead less
Interactions Between Developmental NMDA Receptor Dysfunction, Genetic Vulnerability And Early-life Stress In Schizophrenia: Studies Of Dysbindin Mutant Mice And Living Individuals At High Risk Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$347,457.00
Summary
This project will investigate two key pathways implicated in schizophrenia: glutamatergic (excitatory) neurotransmission and stress signalling. We will study how glutamatergic deficits emerge across postnatal development, in the presence or absence of early-life stress, in a schizophrenia-relevant mouse model, and investigate the interactions between stress and glutamatergic deficits in neuroepithelial cells from living individuals at high risk of schizophrenia.
Pathogenesis And Therapeutic Modulation Of Aggressive Behaviour In A Mouse Model Of Autism Spectrum Disorder
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive behaviour is common in autism patients and can have severe consequences on education and employment opportunities. These mice also show excess dampening of brain function (inhibition). This project will test if aggression in these mice is caused by altered inhibition.
Gene-environment Interactions Modulating Cortical And Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$618,300.00
Summary
A feature of many major brain disorders, including schizophrenia and dementia, is disruption of cognition. A key brain area impacted in such cognitive disorders is the prefrontal cortex. This project will use clinically translatable touchscreen to understand how this aspect of brain dysfunction causes abnormal cognition. We will investigate the mechanisms involved, using highly innovative approaches, which will contribute to the development of new treatments for such cognitive disorders.