MSc by Research: m6A modification of segmentation clock mRNAs and its role in somitogenesis

During early embryogenesis, segments (somites) are formed during a process called somitogenesis. These somites will go on to form the bones and muscles of the skeleton. The timing of the segmentation process is regulated by a molecular oscillator, the segmentation clock, that drives cyclic gene expression with a periodicity that matches somite formation. This process is tightly controlled, and dysregulation of the segmentation clock results in diseases such as congenital scoliosis.  

 For the segmentation clock several levels of regulation of clock gene expression are important: transcriptional activation and negative feedback loops, post transcriptional regulation (from splicing to RNA stability) and protein degradation. m6A modification of mRNAs is critical for many post transcriptional processes. It plays an important role during embryonic development and aberrant m6A modification is linked to several diseases. 

This project will investigate how m6A modification controls the segmentation clock and the formation of somites in human induced pluripotent stem cell (hiPSC) derived presomitic mesoderm (PSM) cells as well as in hiPSC derived 3D structures called somitoids. It will provide insights into the mechanisms required for accurate segmentation clock gene expression in embryonic development as well as diseases associated with misregulation of the segmentation clock or the signalling pathways involved such as congenital scoliosis and T-cell acute lymphoblastic leukaemia (T-ALL). 

Aims of the project: 

1. Establish the role of m6A modification for the regulation of segmentation clock expression 
2. Identify regulatory elements in clock gene mRNAs and the proteins that regulate these elements 
3. Establish how this impacts the segmentation clock and 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, microscopy, purification of DNA, RNA and protein, RT-qPCR, Next Generation Sequencing, immuno precipitation, western blotting, mass spectrometry, analysis of large data sets. 

Please see our website for further details on the programme:

Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee

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