Fully funded PhD in regenerative biology – Manchester Bicentenary Studentship

Applying a multidisciplinary approach to uncover the mechanisms underpinning successful regeneration of the spinal cord after injury

About 27 million people worldwide suffer long-term disability following spinal cord injury (SCI) because of our inability to repair the spinal cord (SC). This exciting interdisciplinary project aims at understanding how some species successfully achieve SC regeneration, a long-standing question with profound implications for human health. However, to understand a complex biological process such as spinal cord regeneration, it is important to combine molecular, cellular and tissue level information and to integrate the data in a comprehensive theoretical framework (Chara et al., 2014; Rodrigo Albors et al., 2021; Caliaro et al., 2024).

In this multidisciplinary project, we are proposing to generate experimental data to build a mathematical model to quantitatively integrate parameters at multiple scale: (i) molecular level: determine the role of gene products and signalling pathways known to be important for spinal cord regeneration (ii) cellular level: establish changes in progenitor cells behaviour such as length of the cell cycle, rate and orientation of cell division, and rate of differentiation and (iii) tissue level: rate of spinal regeneration and ability to recover function (swimming and response to stimuli). The specific aims of the project are to:

1- Establish experimentally the cellular parameters that determine the regeneration of the spinal cord in Xenopus

2- Build the first mathematical model of spinal cord regeneration in Xenopus

3- Test experimentally mathematical model predictions using in vivo perturbation

By integrating Crispr-Cas9 in vivo perturbation, imaging at high spatial resolution, machine learning-based image analyses and mathematical modelling, this project will unravel the molecular and cellular mechanisms underpinning spinal cord regeneration. We will establish a robust pipeline combining experimental and theoretical approaches to integrate data at multiple scales that will allow us to simulate tissue dynamics and establish the parameters that are important for spinal cord regeneration.

This multidisciplinary project is a collaboration between the labs of Drs Karel Dorey, Raman Das and Osvaldo Chara.

For more details, visit https://www.findaphd.com/phds/project/bicentenary-applying-a-multidisciplinary-approach-to-uncover-the-mechanisms-underpinning-successful-regeneration-of-the-spinal-cord-after-injury/?p179010

Or contact us via email:

karel.dorey@manchester.ac.uk

osvaldo.chara@nottingham.ac.uk

raman.das@manchester.ac.uk