About the Project
The major glial cells of the peripheral nervous system, myelinating and non-myelinating Schwann cells, are reprogrammed after nerve injury into repair Schwann cells, specialized for maintaining survival of injured neurons, supporting axonal regeneration and nerve repair. This is regulated by Schwann cell-intrinsic signals, yet it is completely unknown whether extrinsic signals from injured axons initiate this process? Before injured axons can regenerate, the segment distal to the injury degenerates within a highly predictable time window. However, Schwann cells respond with changes in transcription long before axonal degeneration, at sites remote from the injury, suggesting potential axonal-Schwann cell signalling.
This project will use a number of cutting edge techniques as well as standard molecular and cell biology approaches to investigate this hypothesis. These include; live imaging of axon-Schwann cell interactions and calcium signalling in transgenic zebrafish models of nerve injury; live imaging of neuronal and Schwann cell populations from transgenic mouse lines in compartmentalized cocultures in microfluidic chambers; and the possibility to use transcriptomics and proteomics along with bioinformatic analysis to identify potential novel signals.
Funding Notes
Funding deadline is 5th December 2018 for start in October 2019. When applying indicate on the application the funding options (GATES USA *deadline 10/10/18*, Gates Cambridge or other Cambridge Funders). Home/EU and International applications are all considered for funding.
Further information can be found on our website https://www-neurosciences.medschl.cam.ac.uk/workandstudy/postgraduate-training/postgraduate-admissions/
References
Arthur-Farraj, P., Latouche, M., Wilton, D.K., Quintes, S., Chabrol, E., Banerjee, A., Woodhoo, A., Jenkins, B., Rahman, M., Turmaine, M., et al. (2012). c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration. Neuron 75, 633–647.
Conforti, L., Gilley, J., and Coleman, M.P. (2014). Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat. Rev. Neurosci. 15, 394–409.
Jessen, K.R., and Mirsky, R. (2016). The repair Schwann cell and its function in regenerating nerves. J Physiol. 594, 3521-3531.
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