Project No. 2401

STANDARD PROJECT

Primary Supervisor

Dr Melissa Andrews – University of Southampton

Co-Supervisor(s)

Prof Arthur Butt – University of Portsmouth

Summary

Maintaining health across the life course requires novel therapies to ensure proper function is always supported.

Maintaining health across the life course requires novel therapies to ensure proper function is always supported. In the central nervous system (CNS; brain and spinal cord) in particular, irreversible neurodegeneration and irrevocable loss of function can occur following an accident, vascular event, sports injury and is part of the normal course of ageing. Axon regeneration, however, does not occur because glial cells form an inhibitory scar tissue that terminates axon growth. Cell transplantation has helped to replace damaged cells and promote repair. In this context, olfactory ensheathing cells (OECs) are specialised glial cells that provide trophic factors and cellular bridges for growth of olfactory axons into the brain throughout life. Also promising for regenerative growth is re-expression of integrin receptors, which are essential for neuronal outgrowth and axonal pathfinding during development but are downregulated with maturation. Re-expression of integrin receptors using viral vectors results in sensory axon regeneration, however integrins do not transport effectively from cell body to axon/growth cone within the main motor pathway, the corticospinal tract, minimising their growth-promoting ability. Targeting integrins to axons, however, requires further development.

We have previously developed integrin-expressing exosomes from HEK293 cells that induce significant outgrowth in cultured dorsal root ganglia on inhibitory substrates. The aim of this studentship is to engineer exosomes from a direct physiological source (OECs) for targeted delivery of growth-promoting receptors including integrins. The project will provide training in exosome development and cellular assays to test the hypothesis that integrin-expressing exosomes derived from neural sources will induce significant growth in primary neurons grown on inhibitory extracellular matrix, ex vivo brain slice and spinal cord slice models.

The outcomes of this studentship will provide new technologies for targeted delivery of functional molecules which will build up a greater understanding of healthy ageing and its challenges within the nervous system.

Candidates with a strong interest in neuronal cell biology, microscopic imaging, and regenerative medicine are encouraged to apply.