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Molecular and cell-biological mechanisms mediating establishment of neuron polarity during development


Faculty of Biology, Medicine and Health

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Dr R Das , Dr C Francavilla Applications accepted all year round Self-Funded PhD Students Only

About the Project

Background

Cells undergoing neuronal differentiation in the embryonic spinal cord delaminate from the neuroepithelium, resulting in loss of apical cell polarity. This is a potentially hazardous cell state, requiring tight control, as the nascent neuron must now rapidly re-establish its polarity. This repolarisation is crucial, as it determines the position of axon outgrowth, an important step in establishment of normal tissue architecture and formation of functional neural circuitry. Errors in this critical process lead to a number of neurodevelopmental disorders and have also recently been identified as one of the earliest indicators of dementias such as Alzheimer’s and Huntington’s disease.

Details of the project

This project builds on our recent discovery of a new form of cell sub-division (apical abscission) that mediates acute loss of cell polarity in cells undergoing neuronal differentiation (Science, 2014). How these neurons re-establish their polarity and subsequently extend an axon in the correct orientation is now a key question in the field. This project is highly interdisciplinary and will integrate pioneering cell and developmental biology techniques with powerful quantitative Mass Spectrometry-based proteomics. Specifically, the successful candidate will utilise cutting-edge live-tissue imaging techniques to visualise and manipulate key polarity-inducing factors during neuron repolarisation. Proteomics will then be employed to identify novel molecular determinants that interact with polarity-inducing factors to influence neuron repolarisation.

Overall this project lies at the critical interface between cell and developmental biology and is therefore likely to provide physiologically relevant insights into the molecular mechanisms leading to neuron polarisation and axon extension.


Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).

Informal enquiries may be made directly to the primary supervisor.

References

R. M. Das, K. G. Storey, Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343, 200-204 (2014).

R. M. Das, A. C. Wilcock, J. R. Swedlow, K. G. Storey, High-resolution live imaging of cell behavior in the developing neuroepithelium. Journal of visualized experiments: JoVE, (2012).

Francavilla C., et al., Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs. Molecular Cell 51, 707-722 (2013)
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