Studying microRNA landscape during spinal cord regeneration

About the Project

The human spinal cord (SC) has limited regenerative capacity, and no effective therapies exist to restore function after spinal cord injury (SCI), resulting in severe disability and low quality of life and life-expectancy. In non-regenerative species, damaged axons fail to regrow, and neural stem/progenitor cell (NSPC) proliferation primarily contributes to scar formation. In contrast, regenerative species such as Xenopus and zebrafish restore axonal continuity, with NSPCs mounting a rapid proliferative response that leads to neurogenesis. These processes are governed by dynamic interactions between transcription factors (TFs) and regulatory molecules such as microRNAs. My work has shown that microRNAs are key to tune the dynamic expression of TF during developmental neurogenesis. MicroRNAs are present in SC and SC fluid (SCF), and their expression is dysregulated after SCI, suggesting that they play a role in this pathogenesis. Most microRNA data come from SC tissue or SCF in non-regenerative species, with limited knowledge in regenerative models, which has only been evaluated in SC tissue at single timepoint. A member of our team has pioneer the extraction of Xenopus SCF undergoing regeneration, technique that will provide information to use cross-regenerative species. We hypothesize that SCI induces dynamic changes in the microRNA landscape of both NSPCs and SCF that promote a permissive environment for regeneration. To validate this hypothesis, you will (1) perform a high-throughput microRNA and mRNA sequencing analysis of NSPCs and SCF at different timepoints from regenerative and non-regenerative Xenopus stages, (2) identify candidates and validate differentially expressed microRNA-mRNA nodes using RT-qPCR to comprehensively understand the microRNA-mRNA landscape changes after SCI, (3) conduct cross-species studies to understand the conserved underlaying mechanism of validated microRNA after SCI. Molecular, genetic, and imaging approaches, including CRISPR-Cas9 mutagenesis, in situ hybridization, immunostaining, and live microscopy, and xenopus and zebrafish spinal cord injury will be used for this study.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in zebrafish and/or xenopus, molecular biology and confocal imaging, are particularly encouraged to apply.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants mustmake 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 3 (high) fee. Details of our different fee bands can be found on our website View Website