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The Role of cell adhesion proteins in healthy and cancerous epithelial cells


   Faculty of Biology, Medicine and Health


About the Project

Correct wiring of neuronal axons after nerve injury is a prerequisite for recovery of function. Following spinal cord or peripheral nerve trauma there is impaired axon regrowth, indeed only half of all axons will cross a surgical repair site and even fewer reach their target organ. Therefore knowledge about how one can promote outgrowth in a targeted manner is key for improvement of surgical peripheral nerve repair.
On their way through nervous tissue, axons are guided by a variety of guidance cues. A key element in guiding growing axons is the extracellular matrix (ECM). Axons specifically bind to the ECM by the integrin family of adhesion receptors, which in neuronal cells are organised into special structures known as point contacts (PCs). Forces required for axon outgrowth are very likely transmitted to the ECM via these PCs; however, how PC signaling contributes to axon outgrowth and pathfinding is unknown.
Growth cones at the tip of the main axon are the sensory regions of developing neurons that enable axon pathfinding and target recognition. They express adhesion receptors, the integrins, that connect the intracellular actin cytoskeleton to the surrounding ECM and thus permit protrusion. Awareness that integrins can provide key signals for axon growth and guidance has emerged only recently and how they collaborate with other guidance factors to pathfinding and regeneration processes is unknown.
Therefore, the key objective of this project will be to provide a better understanding of how different ECM proteins contribute to axon outgrowth and pathfinding thereby permitting the development of novel materials for enhanced nerve regeneration. We will use high resolution bioprinting to create precisely defined ECM patterns and test how they influence axon outgrowth and pathfinding. We combine this technology with advanced imaging and molecular biology techniques to gain insight in the molecular mechanisms of pathfinding.

Training/techniques to be provided:
Advanced fluorescence microscopy, molecular biology, substrate engineering (micro-patterning)

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject ideally with extensive practical experience (e.g. through Masters or placement study). Candidates with experience in Cell Biology are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Miller, K.E. and D.M. Suter, An Integrated Cytoskeletal Model of Neurite Outgrowth. Front Cell Neurosci, 2018. 12: p. 447.

Lowery, L.A. and D. Van Vactor, The trip of the tip: understanding the growth cone machinery. Nat Rev Mol Cell Biol, 2009. 10(5): p. 332-43.

Melero, C., Kolmogorova, A., Atherton, P., Derby, B., Reid, A., Jansen, K., Ballestrem, C., Light-Induced Molecular Adsorption of Proteins Using the PRIMO System for Micro-Patterning to Study Cell Responses to Extracellular Matrix Proteins. JOVE, 2019.
de Luca A, Faroni A, Reid AJ., Dorsal root ganglia neurons and differentiated adipose-derived stem cells: an in vitro co-culture model to study peripheral nerve regeneration JoVE 2015; 26:(96).

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