The Role Of The Ras Signalling Molecule, C3G, In The Interaction Of Neural Precursor Cells And Their Environment
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
Developmental brain disorders affect 1-3% of the population. The mental retardation disease spectrum includes neuronal migration disorders and neural precursor proliferation disorders. We propose to study a molecular mechanism regulating neuronal migration, survival and proliferation. We have identified a protein, C3G, which is essential for three aspects of nervous system development: (A) C3G limits neural precursor cell proliferation. (B) C3G is essential for neuronal survival. (C) C3G is cruc ....Developmental brain disorders affect 1-3% of the population. The mental retardation disease spectrum includes neuronal migration disorders and neural precursor proliferation disorders. We propose to study a molecular mechanism regulating neuronal migration, survival and proliferation. We have identified a protein, C3G, which is essential for three aspects of nervous system development: (A) C3G limits neural precursor cell proliferation. (B) C3G is essential for neuronal survival. (C) C3G is crucial for neuronal migration. C3G acts in a cascade of proteins, known as the Ras signalling pathway, which transmits signals from the extracellular environment into the cell nucleus to elicit appropriate responses of the cell to cues from the outside. We will identify proteins that, together with C3G, affect the important processes of neural precursor proliferation, and neuron survival and migration. This project will fully characterise a key regulatory mechanism of cellular processes crucial to the development of normal intelligence.Read moreRead less
Developmental Neurobiology Of Schizophrenia And Translation Into New Treatments
Funder
National Health and Medical Research Council
Funding Amount
$611,574.00
Summary
Our ultimate goal is to expand effective treatment options for people with schizophrenia particularly ones that can prevent schizophrenia from developing. The successful completion of this project will identify novel biological pathways by which schizophrenia develops and, importantly, will yield new molecular tools to personalise treatment of schizophrenia.
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
Identification Of Genes For Non-syndromic Intellectual Disability And Walker-Warburg Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$399,984.00
Summary
Mental retardation (MR) affects 3% of people and the cause is still largely unknown. Walker-Warburg syndrome (WWS) is an inherited cause of severe MR that also includes eye and muscle disease. Recent studies suggest that there are at least ten WWS genes. This project will identify MR and WWS genes by searching for gene alteration (mutations) that affected families have in common. Knowledge of the genetic causes will lead to better understanding of normal brain development and therapies.
Decoding Conserved Mechanisms That Control Neuronal Migration
Funder
National Health and Medical Research Council
Funding Amount
$526,950.00
Summary
During brain development, nerve cells interact with each other and their surrounding environment through a forest of molecules that are essential for precise cellular communication. Deficient signaling between these molecules causes defects in development and leads to disease. By employing genetic and biochemical approaches we propose to identify new mechanisms through which the brain develops, to better understand how brain diseases such as epilepsy and schizophrenia occur.
Growth factors are essential molecules for normal brain development. Variations in the amount of the different growth factors have been implicated in such diseases as AlzheimerÍs and ParkinsonÍs disease. This project will study the precursor of a growth factor known as brain derived neurotrophic factor (BDNF) and what specific roles the precursor might play in brain development.
Understanding The Embryonic Origins Of Cortical Malformations
Funder
National Health and Medical Research Council
Funding Amount
$815,228.00
Summary
Cortical malformation leads to mental retardation and epilepsy. Identification of the aberrant developmental processes contributing to these devastating syndromes is essential for accurate clinical assessment and development of novel therapeutics. Here we investigate a developmentally important receptor, Neogenin, which when mutated, leads to cortical malformations. Determining how Neogenin functions is expected to uncover new signaling pathways contributing to these malformations.
Targeting Autism With Macrocephaly Using Mechanism Based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$831,652.00
Summary
Autism affects a large number of children in our community and currently there is a lack of any medication to treat its core pathology. In this grant we will study the underlying biochemical changes in the brain that result in autism through the development of a new mouse model of the disorder. This mouse model will then be used test drugs to identify therapeutic targets for the treatment of autism.
The Importance Of Superstars: Cell Numbers And Lineages In Enteric Nervous System Formation
Funder
National Health and Medical Research Council
Funding Amount
$561,717.00
Summary
All digestive functions are controlled by a nerve system in the gut wall, and it works without us thinking about it. This is a huge system rivalling the spinal cord in number of nerve cells. And it has may different types of nerve cells. It originates from a very few cells early in the embryo, about 200 times fewer than the spinal cord. How do the cells manage to divide enough to make this system, and how do they 'know' how to make the right types of nerve cells in the right places in the gut?