4 YEAR PhD IN NEUROSCIENCE
Peripheral nerve regeneration and cancer
The peripheral nervous system is one of the few tissues in the mammalian adult, which is capable of extensive regeneration. This process is all the more remarkable, in that repair can reconnect and re-establish fully transected nerves – requiring both the production of new tissue to bridge the gap between the nerve stumps and the accurate direction of regrowing axons back to their targets. Schwann cells are known to play a pivotal role in this process. In the adult, these highly specialised cells are normally in a quiescent state, myelinating larger axons or bundling together groups of smaller axons. Upon injury however, they dedifferentiate en masse to a progenitor/stem-like state and the proliferation and organisation of these cells is known to be critical for the repair process. Schwann cell number and state is strictly controlled by the axon both during development and following repair. Imbalances in this tightly regulated system would be predicted to result in either degenerative disorders or hyperproliferative disorders such as cancer. Consistent with this view, Schwann cell tumours, especially neurofibromas, resemble an unrepaired wounded nerve, in that Schwann cells within the tumours are dedifferentiated and proliferate in the absence of axonal contact in a mixture of fibroblasts and inflammatory cells.
Projects in the lab would be in one of the following areas.
- Understanding the plasticity of the Schwann cell differentiation state
- Schwann cell/axonal interactions during repair and cancer
- Novel mouse models for studying tumour development in NF1
- Role of the microenvironement in the repair process and cancer.
For more detail about potential projects, candidates are advised to contact the lab directly.
Simona Parrinello, Ilaria Napoli, Sara Ribeiro, Patrick Wingfield Digby, Marina Fedorova, David B. Parkinson, Robin D. S. Doddrell, Masanori Nakayama, Ralf H. Adams and Alison C. Lloyd (2010)
EphB signalling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting.
Cell 143 (1): 145-155
Simona Parrinello and Alison C Lloyd. (2009)
Neurofibroma development in NF1 – insights into tumour initiation
Trends in Cell Biology 19 395-403
Simona Parrinello, Luke A Noon, Marie C Harrisingh, Patrick Wingfield Digby, Pedro Echave, Catherine A Cremona, Laura Rosenberg, Adrienne M Flanagan, Luis Parada and Alison C Lloyd. (2008)
NF1 loss impairs Schwann cell-axonal interactions: a novel role for semaphorin 4F
Genes and Development 22 3335-3348
Harrisingh MC, Perez-Nadales E, Parkinson DB, Malcolm DS, Mudge AW and Lloyd AC. (2004)
The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation
EMBO J 23, 3061-3071
Mathon, N.F, Malcolm DS, Harrisingh MC, Cheng L, Lloyd AC. (2001)
Lack of replicative senescence in normal rodent glia.
Science 291, 872-875