Centre for Brain Research

Aoteoroa Neuroscience Postdoctoral Fellow Projects

The role of GABAergic inhibition in motor recovery early after stroke

CBR PIs?AIs: Professor Winston Byblow, Dr Cathy Stinear, Dr Suzanne Ackerley, Dr James Coxon, Professor Alan Barber

This project builds upon a decade of research undertaken by the PIs on stroke recovery and rehabilitation and capitalises on various strengths, across clinical neuroscience, neuroimaging and neurological rehabilitation within the Centre for Brain Research and the Brain Recovery Clinic.

The effectiveness of applied rehabilitation therapies is diminished by the relative lack of knowledge regarding the physiology of motor recovery, and this acts as a barrier to the restoration of function. Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter. GABAergic inhibition affects neural plasticity, motor learning, and recovery after stroke. In patients at the chronic stage of stroke, interventions that are thought to reduce tonic GABAergic inhibition in human primary motor cortex (M1) lead to better functional outcomes. This new project will examine the trajectory of M1 GABAergic inhibition in human patients during the initial weeks after stroke, and whether it is open to modification at various time points using non-invasive brain stimulation (NIBS), such as rTMS and TDCS.

The aim of this project is to explore the contribution of disinhibition to spontaneous recovery after stroke, and whether it can be altered by neuromodulation. Achieving this aim will provide a principled basis for future trials to test whether NIBS can be used in an individualised way to promote recovery after stroke. We have two objectives:

  1. To test our theory that motor recovery in human patients is mediated is by tonic inhibitory tone.
  2. To generate proof of principle evidence that M1 inhibition is modifiable by NIBS during spontaneous recovery, and that this can be targeted to individual patients.

The role of the postdoctoral fellow would be ideally suited for a PhD with experience in human neurophysiology and brain imaging and neurological rehabilitation. Experience with clinical populations, TMS, MRI/ MRS is highly desirable.

For more information about this project please contact Professor Winston Byblow: w.byblow@auckland.ac.nz

Drugs for neurodegenerative disorders

CBR PIs: Professor Mike Dragunow and Professor Margaret Brimble 

Currently there are no effective disease-modifying drugs to treat neurodegenerative disorders. We have launched a new drug discovery platform to test potential medications for human neurodegenerative disorders. The platform consists of adult human brain cell culture and high content screening facilities to directly test compounds on human brain cells with the aim of identifying novel drug leads which can potentially be developed into pharmaceutical candidates. This testing facility, which is closely linked with the Brimble natural product and medicinal chemistry laboratories and the CBR Biobank, is now up and running and currently screening compounds from the Brimble Natural Product Library. The role of the postdoctoral fellow will be to fully engage in this screening program and work with the Dragunow and Brimble groups and the Biobank research technicians to enhance current assays (eg: brain inflammation assays), develop novel assays (eg: protein misfolding assays) and identify compounds for further medicinal chemistry development. Ideally the candidate will have a strong background in neuroscience, molecular pharmacology and high content screening and expertise in mammalian cell culture and molecular biology techniques. Interested applicants should contact Professor Dragunow for further information m.dragunow@auckland.ac.nz.


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 m.curtis@auckland.ac.nz