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The mechanism of forelimb dystonia in mice with the ADNFLE human epilepsy mutation
| Florey Neuroscience Institutes |
The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby mutations produce seizures is unknown.  View project details
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The Role of BMP Receptor IA in Neural Stem Cell Differentiation
| Florey Neuroscience Institutes |
In this project, you will perform cell culture assays with primary cultures of neural stem cells derived from the subventricular zone of adult mice to examine the role that BMP receptor IA plays in the proliferation and differentiation of neural stem cells.  View project details
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The Role of BMP signaling in the Neural Stem Cell Response to Demyelination
| Florey Neuroscience Institutes |
Supervisors:Dr. Holly Cate and Professor Trevor Kilpatrick
Chronic demyelinating diseases are characterized by the death of oligodendrocytes, the myelin forming cells of the central nervous system. We are investigating ways to replace these lost cells to increase repair following myelin damage. Stem cells in the adult brain can produce oligodendrocytes, but this process is inefficient in the injured brain. We have used microarray technology to examine the molecular changes in brain stem cells during myelin damage to identify the natural responses to demyelination that may influence oligodendrocyte production. Our work has revealed that the level of Bone Morphogenic Protein 4 (BMP4) is elevated in the brain during myelin damage and that elevated BMP4 decreases the production of oligodendrocytes from stem cells in the adult brain. We are currently using cell culture assays and mouse models of demyelination to investigate the role that BMP4 plays in inhibiting remyelination. We have found that BMP4 affects adult brain stem cells by biasing the population toward astrocyte production and away from oligodendrocyte production. Our results suggest that BMP signaling plays an important role in influencing the activity of brain stem cells during a demyelinating insult and that the influence of BMP is likely to inhibit repair. We have found that we can alter the activity of BMP4 in animal models of demyelination by using a naturally occurring inhibitor of BMP (called Noggin) and are currently investigating the therapeutic potential of blocking BMP signalling during the timecourse of demyelination and myelin repair. We hypothesize that blocking BMP4 pathway during and/or following myelin damage will enhance repair by blocking the inhibition of oligodendrocyte production.  View project details
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The role of GDNF family ligands in the choice of target in the sympathetic innervation of the gut
Sympathetic neurons innervate smooth muscle, ganglia and blood vessels in the gut. Different subclasses of sympathetic neuron connect to each of the three classes of target. This project examines how each type of neuron is guided to the correct target.  View project details
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The role of GFRα receptors and ret in the development of sympathetic neurons
The GDNF family of ligands plays an important part in the differentiation, axon projection and survival of sympathetic neurons. GFRα receptors, together with ret, form the receptor system through which all members of this family signal, so that understanding their distribution on the different types of sympathetic neuron is crucial to understanding what the receptors do.  View project details
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