China Scholarship Council: Somitogenesis and the cell cycle


   School of Life Sciences

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  Prof J K Dale, Dr P Murray  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

One of the key processes in embryo development is somitogenesis. This describes the formation of segments, known as somites, that go on to develop the bone and muscles of the skeleton. The timing of this process is regulated by a molecular oscillator, the segmentation clock, that regulates the oscillatory expression of several genes, the clock genes. The periodicity of the expression of the clock genes matches the periodicity of somite production (1). The Notch signalling pathway is one of the key pathways required for this process. Notch is activated by receiving a signal from a neighbouring cell, which results in the cleavage of the Notch transmembrane protein and the release of Notch intracellular domain (NICD) which translocates to the nucleus where it regulates the expression of several clock genes. Negative feedback loops ensure that NICD levels also oscillate in time with somite formation (2). 

Recent data from the Dale lab shows that in human induced pluripotent stem cells (hiPSC) derived presomitic mesoderm cells (PSM) levels of NICD are dependent on the stage of the cell cycle. Moreover, in MCF7 cells (a breast cancer line) it has been shown that the length of the cell cycle is dependent on the levels of a clock gene when the cell begins mitosis (3). Together, these and other studies indicate a complex interaction between the cell cycle and dynamic Notch signalling. 

This project will investigate the mechanisms that link the cell cycle to the segmentation clock and how manipulation of the factors involved affect the segmentation clock and somitogenesis in hiPSC derived PSM cells as well as in hiPSC derived 3D structures called somitoids. 

Aims of the project: 

  1. Establish the relationship between the cell cycle and the segmentation clock 
  2. Identify the key cell cycle regulators involved in this autoregulatory loop 
  3. Determine how misregulation of these factors affects somitogenesis 

Examples of techniques expected to be used during the project: maintenance of hiPSC, CRISPR modification of hiPSC, differentiation of hiPSC into PSM cells, generation of hiPSC derived somitoids, immuno fluorescence, in situ hybridisation, 

FACS, microscopy (e.g. time lapse imaging, confocal), purification of DNA, RNA and protein, RT-qPCR, Next Generation Sequencing (e.g. RNAseq, ChIPseq, scSeq), immuno precipitation, western blotting, mass spectrometry, analysis of large data sets, mathematical modelling. 

Biological Sciences (4)

Funding Notes

In order to be eligible for these awards applicants must:
Be a Chinese national
Meet the requirements of the CSC – please see their website
Hold an unconditional offer to study for a PhD at the University of Dundee and meet our English language requirements
Have completed a bachelors or masters degree before the agreed start of PhD study.
Already have an IELTS score of 6.5 at time of applying
For further information on the CSC programme please visit https://www.dundee.ac.uk/phds/funding/china-scholarship-council-csc-programme and apply by completing our application form - https://dundee.onlinesurveys.ac.uk/csc-programme-2024-entry

References

References
1) Carraco G, Martins-Jesus AP, Andrade RP. (2022) The vertebrate Embryo Clock: Common players dancing to a different beat. Front Cell Dev Biol. 10: 944016.
2) Kopan R and Ilagan MXG (2009) The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism. Cell 137: 216.
3) Sabherwal N , Rowntree A, Marinopoulou E, Pettini T, Hourihane S, Thomas R, Soto X, Kursawe J and Papalopulu N (2021) Differential phase register of Hes1 oscillations with mitoses underlies cell-cycle heterogeneity in ER+ breast cancer cells. PNAS 118, e2113527118.

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