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Transcriptional control of CNS myelination
| Florey Neuroscience Institutes |
Co-Supervisor: Prof Trevor Kilpatrick
Myelination of the vertebrate CNS is vital for its proper functioning, as evidenced by the severe effects of human demyelinating diseases such as Multiple Sclerosis. The myelination process is under tight transcriptional regulation, both during development and during repair following a demyelinating insult. This project will investigate the roles of a recently described transcriptional regulator of CNS myelination, Myelin Gene Regulatory Factor (MRF), in developmental myelination as well as myelin maintenance and myelin repair in the adult CNS.  View project details
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Transcriptional control of nervous system development
| Florey Neuroscience Institutes |
The formation of the brain involves the production of many different kinds of neurons that must be positioned very precisely so that they can contact other neurons and integrate into functional neuronal circuits. New neurons are always generated at a distance from their final locations and they must travel along very specific routes in the developing brain to reach these locations (Merot et al, 2009). This process of neuronal migration is of considerable importance for the correct development of the brain, since mutations in genes that cause migration defects in the cerebral cortex during foetal life often result in severe mental retardation.
Our goal is to identify the key steps that control neuron production and cell migration within the developing brain, with an emphasis on uncovering novel genes which are essential to these processes. Through this research, we may be able to better understand the impact of genetic and environmental factors on brain formation and connectivity, and then to apply this knowledge to explain the consequences of abnormal development on subsequent brain function. Our research also focuses on identifying and characterising genes that are associated with the etiology of autism and mental retardation, as well as brain disorders such as schizophrenia and bipolar disorder.
View project details
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Transgenic approaches to understand the function of angiotensin in the brain.
Angiotensin is a crucial molecule for regulation of blood pressure and a target of several of the major frontline treatments for cardiovascular diseases. We have shown that angiotensin II acts in the brain to excite neurons that regulate sympathetic activity (2). Our evidence also indicates that this activity is increased in cardiovascular diseases. To date it has not been possible to selectively knockout the angiotensin receptors from specific groups of neurons in particular brain regions. We now have a transgenic mouse with loxP sites flanking the AT1A receptor and have shown that using cell-specific expression of cre-recombinase we can efficiently delete receptor expression (Gurley, Allen et al., Nature Medicine (submitted)). Using both transgenic mice and cell-selective viruses expressing Cre this project will examine the functional response to AT1A receptor knockout from specific brain regions. View project details
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Transplantation and integration of post-mitotic cortical interneurons
| Florey Neuroscience Institutes |
There is widespread interest in transplantation strategies for treatment of a damaged nervous system. Interneuron progenitors integrate and form functional circuits in a post-natal cortex, but it is unclear whether migrating, post-mitotic interneurons maintain this capacity. This project is designed to determine whether the integration capacity of transplanted interneurons is dependant on developmental stage. View project details
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Transplantation of brain precursor cells and stem cells
| Florey Neuroscience Institutes |
Where do neurons go and what do they become in the immature brain? What kinds of brain cells do purified stem cells give rise to? To answer these questions, we have combined genetic marking with brain transplantation techniques. View project details
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