Clinical Research; Research Networks; Laboratory Based Research


Click on each link below to find out more:

Behavioural research (led by Prof Steve Dunnett)
Clinical neuroscience (led by Prof Anne Rosser)
Genetics research group/stemcell theraphy (led by Dr Nick Allen)
Molecular research (led by Dr Lesley Jones)

Clinical neuroscience (led by Prof Anne Rosser)

Neural transplantation for Huntington’s disease is an attractive therapy for this devastating neurodegenerative disease which affects in particular the medium spiny neurons of the striatum. Within the lab we are interested in many aspects of the disease and have a multidisciplinary approach incorporating molecular biology, neural transplantation and neuropsychology.
The successful clinical trials of transplantation have to date all used embryonic donor tissues. However, whereas surgeries based on using human embryonic tissues can provide a 'proof of principle' the long term development and wider availability of neural transplantation is critically dependent on the identification of more readily available alternative sources of cells. We are actively exploring expanded populations of human stem and precursor cells, xenografts, and genetically manipulated cells and cell lines for their ability to provide safer and more readily available alternative to primary embryonic neurones for transplantation.  As part of this we need to optimize the yield of medium spiny neurons from our cultures which will involve various cell culture manipulations.
Understanding the mechanism of gene expression changes of a particular population of cells in culture over time as well as changes in the developing striatum may help to identify specific factors that may be influential in how we culture cells to generate a specific population of cells i.e. medium spiny neurons for transplantation in HD.
Another important factor for transplantation is to improve the yield of surviving cells during transplantation and so we are exploring methods to optimize the transplantation protocol. Critical factors involve identification, dissection and handling of embryonic donor cells, and the surgical implantation protocols that maximise accuracy of placement and minimise trauma both to the host and to the implants.
A complementary approach to cell transplantation (which involves replacing cells once already lost) is to protect damaged or traumatised neurones of the host brain from the assault of injury or disease. A wide number of compounds have been identified which have the potential to block processes of cell death and to promote regrowth of damaged cells, including growth factors, antiapoptotic agents, antioxidants and transcription factors. However a common problem for their use is that they don't cross over into the brain when injected or ingested peripherally. We are developing ways to deliver neuroprotective agents into precise sites in the brain both by engineering cells for transplantation ('ex vivo gene therapy') and by using viral vectors for direct intracerebral delivery ('in vivo gene therapy').

Scientific group members:
Anne Rosser
Claire Kelly
Sophie Precious
Ngoc Nga Vinh
Rike Zietlow

Human foetal tissue will expand in culture as neurospheres.	On removal of specific factors from the medium these cells can differentiate into neurons and astrocytes.
Immunohistochemistry with specific antibodies allows the characterization of these cultures, neurons are labeled red and astrocytes are labeled green.