About the Project
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.
Informal enquiries may be made directly to the primary supervisor.
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)
Based on your current searches we recommend the following search filters.
Based on your current search criteria we thought you might be interested in these.