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Centre for Brain Research
Aotearoa Neuroscience Postdoctoral Fellow
Projects
1. » The localisation and function of the inhibitory system in neural
plasticity and diseases of the human brain.
2. » Mechanisms and treatments for deficits in cortical development
and cognition in survivors of preterm birth
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The localisation and function of the inhibitory system in
neural plasticity and diseases of the human brain.
CBR PIs: Dr Maurice A Curtis and Dr Henry J Waldvogel
The inhibitory system in the human brain plays a critical role during
development and continues to impact on normal brain function as well as
being a major drug target for known neuroactive pharmaceuticals and in
novel drug design. How the inhibitory system works in the normal brain,
and how it is altered in brain diseases, is well studied but poorly
understood. In this project we will study the localisation, mechanism of
action and function of the postsynaptic protein complex at inhibitory
synapses in normal and diseased conditions. We also propose to study the
role of the inhibitory system in structural plasticity and neurogenesis in
the human brain cells and tissue.
This research project will use immunohistochemical methods and high
resolution imaging techniques to characterize the inhibitory synapses in
the adult human brain and to study the complex anatomical localisation.
We propose to use cell culture to alter the distribution of glycinergic and
GABAergic proteins followed by gene expression profiling of associated
genes and their products. In addition we propose to use live receptor
labelling techniques to track receptor formation and recycling in human
and rodent cell lines know to express high levels of inhibitory synapses
and receptors. This research plan is a clear ambitious progression from
current studies into the neurobiology of the glycinergic and GABAergic
postsynaptic complexes. We are characterising the localisation and
plasticity of inhibitory receptor synaptic complexes throughout the entire
human brain. To delineate the postsynaptic complexity, we will adopt an
interdisciplinary approach to study the distribution and co-localisation of
postsynaptic proteins with glycinergic, GABAA and GABAB receptor
subunits and scaffolding proteins such as gephyrin as well as other
important receptors such as dopaminergic receptors in post-mortem adult
human brain and spinal cord.
To date few studies have reported on the presence of inhibitory receptor
proteins in the neurogenic and high plasticity areas of the human brain.
This system is thought also to play a large role in neuronal migration and
development. In addition, given that many neuroleptics, antipsychotics
and antidepressants alter the inhibitory system it will be important to
identify areas that these drugs may be targeting and to identify new
targets for novel drug discovery in the human brain. Our approach will be
to use a wide range of techniques and to have a multidisciplinary
approach including genetics, pharmacology, neuroanatomy as well a
variety of specialist imaging techniques.
Interested applicants should contact Dr Maurice Curtis for further
information [email protected]
Mechanisms and treatments for deficits in cortical
development and cognition in survivors of preterm birth
CBR PIs: Dr Justin Dean; Professor Alistair Gunn; Professor Laura
Bennet
Preterm born infants have very high rates of neurological disability,
including deficits in learning, memory and cognition that persist into
adolescence and adulthood. These deficits are strongly associated
impaired growth of grey matter structures of the brain, including the
cerebral cortex. In a preclinical model of brain ischemia in preterm fetal
sheep, we recently found that these deficits in grey matter growth were
driven by impaired growth of dendrites and synapses of neurons, rather
than neuronal cell death. This overturns the long-held belief that low
blood flow to the developing brain kills causes death of neurons. Rather, it
disrupts the ability of these cells to grow and mature correctly. This opens
new avenues for potential therapies to promote regeneration and repair of
the premature brain.
We are looking to support a postdoctoral fellow in studies aimed at
understanding the mechanisms of impaired neuronal development
following preterm ischemia, and in developing therapeutic strategies
targeted at restoring normal brain growth and function.
Interested applicants should contact Dr Justin Dean for further
information [email protected]