4-year MRC-DTP PhD position in Spinal cord regeneration, University of Manchester

Dr. Ximena Soto ( https://research.manchester.ac.uk/en/persons/ximena.soto ) (https://orcid.org/0000-0003-2680-1837 ) is looking for a PhD student enthusiastic and keen on using Zebrafish to elucidate the signals and mechanisms leading the successful regeneration!.

The Soto lab focuses in the functional importance of dynamic gene expression underlying spinal cord regeneration (SCR) and the mechanism by which microRNAs regulate it using Zebrafish as research organism.

Project description

Spinal cord injury (SCI) paralysis is a devastating disease that affects at least 2500 people per year in the UK. It carries substantial individual and societal costs with most SCI sufferers experiencing chronic pain. No treatments are available to repair SCI. Therefore, there is a need to understand the mechanisms underlaying this process to improve therapies for SCI. Zebrafish is a powerful animal model capable to regenerate SCI. They are able to initiate stem cell proliferation to generate new neurons that replace those lost after spinal cord injury while mammals generate cells that only contribute to scar formation. Elucidating the signals and mechanisms leading the successful regeneration in this model would generate valuable discoveries to be tested in higher organisms. Evidence suggests that upon SCI, progenitor cells reactivate signalling pathways in a dynamic way -oscillatory or pulsatile. These signalling dynamics are influenced by microRNAs(miRs) (a small non-coding RNA) whose expression is tightly controlled upon injury and is important for modulating the expression of multiple genes. To this end, we focus on the functional importance of dynamic gene expression underlying SC regeneration(SCR) and the mechanism by which miRs regulate it using zebrafish as a regenerative animal model. In this project you will:

• Determine the functional importance of Her dynamic gene expression in progenitor cells during SCR.
• Determine the mechanistic effect of miR on Her dynamic protein expression as progenitors change cell fate during SCR
• Identify the molecular components and their interactions for neural progenitors to differentiate during SCR.

Experimental approaches such as molecular biology, genetics, live imaging techniques and zebrafish spinal cord injury will be used for this study. This includes techniques such as molecular cloning, CRISPR-Cas9 mutagenesis and confocal microscopy.

Methods and Training

The PhD project will be based within the Soto lab with co-supervision provided by Manning and Dorey. The Soto lab will provide training in zebrafish, genome editing (CRISPR-Cas9), transgenesis, advance microscopy techniques and image analysis that will underpin the project. There is extensive expertise in these methods in Soto lab, which is also an expert in the study of Her6 dynamic expression during brain development and methods to manipulate and study Her protein dynamic expression. Manning investigates dynamic gene expression in retinal development and ocular disorders using mouse as animal model. The Manning lab will provide training in single cell data analysis and dynamic gene expression. Dr Soto enjoys a productive ongoing collaboration with Dr Manning reflected in the recent publications in Development (2022) and Molecular System Biology (2021). Dorey investigates the mechanisms underpining spinal cord regeneration in Xenopus and focus in unraveling the neurogenic transcriptional trajectory of Neural Progenitor Cells during regeneration. Dorey will provide training in single cell RNA sequencing and data mining. The combined and complementary expertise provided by Soto, Dorey and Manning labs will equip the student with excellent training opportunity.

PROJECT INFORMATION

Funding

The appointed candidates will be fully funded for 4 years and the funds will provide for:

• Tuition fees at the standard UKRI rate (OS candidates accepted, up to a maximum quota of 30%, to be managed by the Board)
• Annual stipend at the minimum UKRI rate (2023/24 rate = £18,622)
• An annual Research Training Support Grant (RTSG) towards project running costs/consumables, conference/workshop attendance, career development opportunities (up to £5,000 per annum).

Eligibility

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

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 – full details on how to apply can be found on the MRC DTP website https://www.bmh.manchester.ac.uk/study/research/mrc-dtp/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team.

Deadline for applications is midnight 10th November 2023

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