Dr Sean Wyatt - PhD
The modality related functional properties of primary afferent sensory neurons of the dorsal root ganglion (DRG) depends partly on their physical characteristics such as axonal calibre, degree of myelination, location of central axonal terminals in the spinal cord and location and degree of arborization of peripheral projections. The molecular phenotype of sensory neurons, in particular the combination of voltage and ligand gated ion channels, neuropeptides, and G-protein-coupled receptors that they express, is also a major determinant of their functional properties.
Neurotrophic factors of the NGF and GDNF families have been shown to be essential for maintaining sensory neuron survival during the embryonic and early postnatal period. In addition, these neurotrophins appear to play crucial roles in modulating the differentiation of different classes of developing sensory neurons, as well as regulating aspects of target field innervation. Whilst these “classic” neurotrophic factors undoubtedly play an important role in regulating the functional properties of sensory neurons in the adult, particularly with regards to molecular phenotype, evidence is beginning to emerge to suggest that other novel neurotrophic factors may also act to modulate the functional phenotype of adult sensory neurons. A loss of appropriate neurotrophic support appears to play an important part in the aetiology of neuropathic conditions such as diabetic neuropathy and neuropathic pain syndromes. In addition, neurotrophic factors also enhance post-trauma repair of damaged peripheral nerves and elevated or inappropriate expression of neurotrophins appears to contribute to the development of pathological inflammatory pain. Therefore, determining how novel neurotrophic factors regulate the functional properties of sensory neurons may have potentially important therapeutic implications.
We use a variety of techniques to investigate whether secreted signalling molecules that have trophic activity in other cell/tissue/organ systems have potentially novel neurotrophic effects on adult DRG neurons. These techniques include primary cell culture, fluorescent image capture and analysis, immuno-histochemistry, confocal microscopy, Western blotting and RT-QPCR. To validate the physiological relevance of in-vitro data demonstrating the efficacy of a novel neurotrophic factor, we are endeavouring to create transgenic model systems that will allow the temporally and spatially controlled deletion of selected target genes as well as spatially and temporally controlled over-expression of “wild type” and modified transgenes.
BBSRC New Investigator award