Ximena Soto Rodriguez

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(MCR DTP) Understanding Spinal Cord Regeneration: The Role of Dynamic Gene Expression

Link on FindAPhD: https://www.findaphd.com/phds/project/mrc-dtp-understanding-spinal-cord-regeneration-the-role-of-dynamic-gene-expression/?p162017

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Personal profile

Overview

My research bridge fields spanning disciplines from developmental biology, regenerative medicine, and computational biology. My multidisciplinary approach explores signals and mechanisms that leads successful spinal cord regeneration, using zebrafish as animal model with regenerative capacity. My research addresses (1) The functional importance of dynamic gene expression underlying spinal cord regeneration, (2) Reactivation of neurogenesis upon spinal cord injury and (3) the mechanism by which microRNAs regulate spinal cord regeneration.

Biography

I am MRC-CDA Fellow in the School of Biological Sciences, Division of Molecular and Cellular Function at the University of Manchester. I am interested in how progenitor cells reactivate upon spinal cord injury to make cell fate decisions generating new neurons, in regenerative species, or astrocytes contributing to scar formation, in non-regenerative species. Furthermore, I am interested in how the reactivated progenitor programs are influenced by microRNAs (miRs) to progress spinal cord regeneration. To address these questions, I develop technology such as Crispr/Cas9-mediated knock-in/out in zebrafish model to perform single-cell live imaging together with quantitative analysis of mRNA and protein expression and mathematical modelling.

 

I completed my PhD in 2006 at the University of Concepcion, Concepcion-Chile supported by the National Commission for Scientific and Technological Research-CONICYT, my PhD work focused in understanding developmental programs involved in early embryogenesis using frog embryos as animal model. My work was centred around chemical-genetic techniques to understand regulatory signal crosstalk in early embryogenesis. From these studies I became fascinated of how cross regulatory signals play key roles in development. I then moved for my first post-doc to the University of Cambridge and University of Manchester where I developed live imaging and wound ablation techniques to study reactivation of developmental signal pathway after injury. My findings unravelled the understanding of balanced dynamic processes involved in wound repair and convinced me of the importance in observing dynamic gene expression and cell behaviour using transparent live organism, therefore it inspired me to pursue my research using zebrafish.

 

I then moved in 2013 for my second post-doc to work together with Nancy Papalopulu to develop my expertise in zebrafish model. My work focused using zebrafish larvae to perform quantitative single-cell techniques and live imaging of neural progenitor cells. My findings contributed to the shift towards dynamic view of cell fate decision fine-tuned by microRNAs. I established a method to generate zebrafish knock-in/out lines using Crispr-Cas9 and state-of-the-art-live imaging of zebrafish embryos with single cell resolution as well as single molecule inexpensive fluorescent in situ hybridisation (smiFISH) for multiple gene single cell quantification. I showed for the first time in the developing zebrafish hindbrain that single cell dynamic expression of the Notch target Her6 (Hes1 in mouse) converts from random expression to pulsatile oscillatory pattern, mediated by the microRNA, miR-9, to enable progenitor cells to undergo cell-state transitions during neurogenesis.

I now want to address the functional importance of dynamic gene expression underlying spinal cord regeneration and the mechanism by which microRNAs regulate it using zebrafish as a regenerative specie.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Beacons, Institutes and Platforms

  • Digital Futures

Keywords

  • Zebrafish
  • Oscillation
  • Neurogenesis
  • live imaging
  • CRISPR/Cas9 mutagenesis
  • Spinal cord regeneration
  • regeneration

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