Projects

Current and recent research projects within the group.

Development of novel, robust 3D CNS tissue models for neurobiological studies and drug discovery

This project aims to develop unique CNS tissue models and then use them to address specific neuroscience questions. It is a collaboration between the OU and TAP Biosystems and will involve an innovative platform technology (RAFT™) for the generation of complex 3D model tissues. The model system will use glial cells and neurons arranged within a hydrogel matrix to resemble living nervous system tissue. These models will be used to monitor the responses of neurons and glia to simulated damage, and to test the effectiveness of this novel approach as a screening technology for potential neuroprotective therapies. The ultimate goal is that this technology will provide researchers in academia and industry with the means to produce robust and reliable tissue models that avoid the cost and variability associated with current 3D culture systems and will reduce their reliance on animal models. The PhD student working on this project is Caitriona O’Rourke.

 

Modelling and overcoming the biological interfaces that prevent nerve regeneration

Biological interfaces in the CNS that inhibit neuronal growth form around implanted spinal cord repair grafts, and at the CNS-PNS boundary. Here we aim to understand and overcome these interfaces in order to improve neuronal regeneration during repair. The approach used is to develop powerful 3D culture models to understand interface formation and persistence. The models are then used as a test-bed for developing novel therapies to overcome inhibitory interfaces and improve spinal cord repair. This is an ongoing collaborative project with Dr Jon Golding’s group. It has received funding from the Wellcome Trust and the postdoctoral researcher who worked on this project between 2007 and 2010 was Dr Emma East.

Developing tissue engineered implantable devices for surgical repair of the peripheral nervous system

This project develops implantable devices for repairing the nervous system using tissue engineering technology. Cells, biomaterials, biochemical and mechanical signals can be combined to build conduits to support neuron growth within damaged peripheral nerves. Prototype devices will be developed and tested using advanced 3-dimensional cell culture models and those with therapeutic potential will be tested in vivo. It brings together the groups of James Phillips (tissue engineering), Jon Golding (stem cells) and Jane Loughlin (myelination) who are part of the new Biomedical Research Network at the OU. The PhD student working on the project is Melanie Georgiou.

Development of biomaterial conduits for peripheral nerve repair

This project builds on our previous experience in the development of tissue engineered conduits for the surgical repair of peripheral nerve injury. We are using new advances in biomaterial design to create conduits that support and guide regenerating neurones. This ongoing research is in collaboration with the Tissue Repair and Engineering Centre at University College London.

Peripheral nerve biomechanics

This project investigates the structural features of peripheral nerves that enable them to bend and stretch during normal movement without compromising their function. Understanding nerve biomechanics will not only give an insight into some fundamental anatomy, it will also be of value to clinicians treating nerve injury and physiotherapists involved in rehabilitation. The project has involved mechanical testing of nerve tissue, electron microscopy to investigate peripheral nerve ultrastructure and ultrasound imaging technologies to study variations in nerve movement at different anatomical locations in human volunteers. It has involved collaboration with physicists, engineers and surgeons and the PhD student currently working on the project is Sarah Mason.

The effects of photodynamic therapy on the nervous system

Clinical observations have led to the suggestion that photodynamic therapy (PDT) may spare the nerve damage which is often associated with the surgical removal of tumours. This could make PDT particularly valuable in the treatment of cancers located within or adjacent to the nervous system. This project has explored the effects of PDT on cells of the nervous system by growing neurones in a 3-dimensional cell culture model to investigate the effects of a panel of photosensitiser drugs. Uptake, metabolism and mode of action of drugs can be studied using fluorescence microscopy, pharmacology and molecular approaches. This project benefits from a collaboration with the National Medical Laser Centre, UCL, providing an applied clinical aspect to a basic science project. The PhD student who worked on this ongoing project until 2009 was Kathleen Wright.

Selective detection and destruction of cancer cells

Cancer cells are often characterised by their rapid rate of division and over-expression of certain proteins, but many normal cells can also divide rapidly and express detectable levels of these same proteins. Consequently, current anti-cancer drugs cannot be used at their most effective concentration, for fear of destroying normal healthy tissues. This project aims to develop PDT approaches that preferentially target cancer cells, allowing tumours to be located and destroyed by focused laser illumination without affecting surrounding healthy tissues. This multidisciplinary project is supervised by James Phillips and Jon Golding in Life Sciences, and James Bruce in Chemistry at the OU, and benefits from collaboration with the National Medical Laser Centre, UCL. The PhD student who worked on this project until 2011 was Stanley Kimani.