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Funded PhD Project in stem cells, mechanobiology and developmental biology

Posted by , on 18 November 2024

Location: University of Sheffield, UK

Closing Date: 6 January 2025

A BBSRC Yorkshire Bioscience DTP-funded PhD project (jointly with the group of Chris Toseland) focusing on the role of biomechanical cues in embryonic cell fate decisions using human pluripotent stem cell differentiation is currently available in the lab of Anestis Tsakiridis, University of Sheffield.

Project description:

The structures that make up the human body trunk, such as the spinal cord and the vertebral column are produced during embryonic development by populations of stem cell-like progenitors (known as neuromesodermal progenitors or NMPs), which are located at the posterior of the embryo. The generation of these progenitors and the cell types they produce is controlled primarily by signalling pathways such as Wnt and Notch. Their disruption leads to impaired NMP production and their derivatives and subsequently disruption of the proper formation of the body trunk, which is often associated with serious birth defects such as spina bifida and vertebral abnormalities. Thus, understanding how signalling pathways direct the induction of NMPs and their distinct derivatives is important for gaining an insight into the causes of such conditions. This PhD project will examine the role of biomechanical cues, such as differential tissue stiffness, in influencing the response of NMPs to different signalling pathways. We will employ human pluripotent stem cell (hPSC) differentiation as a platform for generating in vitro human NMPs and their derivatives, spinal cord and vertebral column cells together with state-of-the-art mechanobiology approaches to address the following questions:
1) How do Wnt/Notch signalling levels correlate with different NMP cell fate decisions and stiffness levels?
2) How are stiffness levels leading to defined cell fates correlate interpreted at the genomic level?
3) How do Wnt/Notch signalling levels correlate with different NMP cell fate decisions and cell confinement levels?

References:

1) Cooper et al. 2024

2) Gogolou et al. 2022

3) Frith et al. 2018

4) Gouti et al. 2014

 

Studentships commence: October 2025

Closing date:  6th January 2025 (17:00 GMT)

To apply see here.

For informal enquiries contact: A.Tsakiridis@sheffield.ac.uk

 

Start date: 1 October 2025

Closing Date: 6 January 2025

Scientific fields: Stem cells, Tissue engineering and organoids, Cell fate control and differentiation, Early embryogenesis, Gene regulation, Morphogenesis, Patterning, Neural development, Signalling, Cell biology, Chromatin and epigenetics, Development and disease

Model systems: Human

Duration: Fixed term

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