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Uncovering the molecular mechanisms underlying spinal cord regeneration


Faculty of Biology, Medicine and Health

About the Project

About 1200 people a year are left paralysed in the UK due to a Spinal Cord Injury (or SCI). This is because injuries involving the central nervous system (CNS) have very poor capacities to regenerate, thus resulting in a permanent loss of function. However, whilst SCI can be devastating to humans the tadpole of the frog Xenopus can regenerate their CNS (spinal cord) completely following amputation or injury. Our goal is to understand how neuronal regeneration occurs in Xenopus to open new therapeutic avenues for patients suffering a SCI or peripheral neuropathies.

Recently, we have identified the transcription factor Foxm1 as being specifically upregulated in the regenerating spinal cord in Xenopus (Pelzer et al. 2020). Our data indicate that Foxm1 has a crucial role in controlling the balance between proliferation and differentiation during spinal cord regeneration by modulating the relative length of the different phases of the cell cycle. Building on these studies, we will characterise the changes in cell cycle dynamics during spinal cord regeneration and uncover the signals controlling the length of each phase of the cell cycle. We will directly test the effect of changing cell cycle dynamics on neuronal differentiation and regeneration. As foxm1 is expressed in the regenerating spinal cord and is crucial for neuronal differentiation, we will determine the intrinsic and extrinsic cues leading to the formation of foxm1+ cells using single cell RNA sequencing experiments. These experiments will also reveal which neuronal types are being generated during early regeneration.

Altogether, these data will establish the molecular and cellular mechanisms leading to the successful recovery of spinal cord function after injury, paving the way to improve neuronal regeneration in mammals.


Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject with at least one year lab experience. Candidates with experience with in vivo work or with an interest in bio-informatic analyses are encouraged to apply.

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. On the online application form select PhD Bioinformatics.

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

Pelzer D., Thuret R., Phipps L., Murtuza Baker S. and Dorey K. (2020) Foxm1 regulates neuronal progenitor fate during spinal cord regeneration (2020) BioRxiv

Phipps L., Marshall L., Dorey K. and Amaya E. (2020) Models for studying regeneration: Xenopus Development 147 (6) dev180844

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