Investigating the impact of nervous system maturation on transmembrane receptor localisation and transport within CNS axons

The mature central nervous system, once fully developed, is a complex integrated system that consists of terminally differentiated cells with cellular and molecular enhancements such as myelination and specialised extracellular matrix giving rise to a fully functional nervous system in the adult mammal. In addition, as genetic modification through gene therapy slowly becomes a realistic treatment option for injury and disease, further knowledge on what
influences the interrelationship between gene therapy and the in vivo and in situ structure of the nervous system is required.

The overarching objective of this project is to determine how the mature nervous system impacts the axonal localization and transport of integrin receptors following viral-mediated expression within central nervous system (CNS) axons. As integrin molecules have been found to induce axon repair, proper localisation of these receptors is critical for therapeutic benefit.

Our aims are:
- Identify the role of the extracellular environment on localization of virally-expressed transmembrane proteins in CNS axons.
- Determine whether modification of virally-expressed transmembrane receptors in CNS axons can override endogenous influences on expression and localization.

To investigate these aims we will use a combination of in vitro tissue culture experiments together with in vivo rodent models of spinal cord injury.