Uncovering the molecular mechanisms underlying spinal cord regeneration

Details

Motor nerves connect the spinal cord and brain with muscles in our face, arms, legs and internal organs. The motor nerves send signals which tell these muscles to contract. When motor nerves go wrong, people experience unpleasant and crippling symptoms, often lasting many years. Curative treatments for such diseases are urgently needed but are currently almost nonexistent.

We know that diseases of motor nerves have varied causes, including diseases such as diabetes or genetic causes. At the University of Manchester, we discovered that mutation in the LRIG2 gene causes urofacial syndrome (UFS), a congenital disease causing grimacing of the face and defects in bladder voiding. Lrig2 mutations prevent normal peripheral nerve patterning and cause functional nerve defects. It is a transmembrane protein thought to regulate growth factor signalling, but very little is known about its biological role(s) in vivo. The goal of this project is to characterise the role of Lrig2 in motor nerve development to help us understand the pathobiology and aetiology of UFS.

We study the role of Lrig2 during the development of nerves in the frog Xenopus tropicalis. Xenopus has unique advantages: it is easy to obtain large number of eggs, which develop externally and are accessible at all stages of development. The genome of Xenopus tropicalis has been sequenced and shows striking similarities with the human genome, meaning that findings from Xenopus provide insight into many human conditions and diseases.

We have developed a frog knockout for lrig2 gene. Initial analyses of the phenotype show that Lrig2 is essential for spinal cord and somite formation. Using this model, we will answer fundamental questions regarding Lrig2 biology: What is its signalling activity? What is the role of Lrig2 during nerve and muscle development? What is its role during mammalian neurogenesis? In turn, these results will inform the logical design of novel therapies to help damaged nerves to grow normally in patients affected by diseases such as UFS.

Eligibility 

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 neuro-biology are encouraged to apply.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Neuroscience Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 (medium) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

References

Pelzer D., Phipps L.S., Thuret R., Gallardo-Dodd C.J., Baker M.S. and Dorey K. (2021) ‘Foxm1 regulates neural progenitor fate during spinal cord regeneration’, EMBO reports. doi: 10.15252/embr.202050932.

Phipps, L.S., Dorey K., and Amaya E. (2020) ‘Model systems for regeneration: Xenopus’, Development, 147(6), p. dev180844. doi: 10.1242/dev.180844.

Roberts NA, Hilton EN, Lopes FM, Singh S, Randles MJ, Gardiner NJ, Chopra K, Coletta R, Bajwa Z, Hall RJ, Yue WW, Schaefer F, Weber S, Henriksson R, Stuart HM, Hedman H, Newman WG, Woolf AS. (2019) Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder Kidney Int. 95(5):1138-1152

Manak I, Gurney AM, McCloskey KD, Woolf AS, Roberts NA. (2020) Dysfunctional bladder neurophysiology in urofacial syndrome Hpse2 mutant mice Neurourol Urodyn. 39(7):1930-1938

Woolf AS, Lopes FM, Ranjzad P, Roberts NA. (2019) Congenital disorders of the human urinary tract: recent insights from genetic and molecular studies. Front Pediatr 7:136