MSc by Research: Function of presomitic mesoderm specific phosphorylation of the Notch intracellular domain in somitogenesis

The Notch signalling pathway is one of the key pathways required for the developing embryo. It is especially important for the process of somitogenesis, the formation of body segments that develop into e.g. the bones and muscle of the skeleton. After receiving a signal from a neighbouring cell, the Notch transmembrane protein is cleaved and the Notch intracellular domain (NICD) is released and translocates to the nucleus where it controls expression of developmental specific gene cohorts. 

Recent research in the JKD lab has identified unique residues in NICD that are phosphorylated in presomitic mesoderm (PSM) cells but are not detected in other cell types. Phosphorylation is a key process in the regulation of the stability of NICD. NICD is more unstable in PSM cells compared to other cell types. This is potentially a really important factor as NICD levels oscillate during somitogenesis, with NICD levels changing from high to low to high again in a 5 hour cycle and the regulation NICD stability is critical for this process. 

This project will be using human induced pluripotent stem (iPS) cells that will be differentiated into PSM cells. This is an in vitro model system for the human embryo. The lab is currently also developing protocols for the generation of gastruloids, stem cell derived 3D structures that form somite like structures that can be used to determine if these phosphorylated residues are critical for somitogenesis. The main aim of this project is to determine the function of the phosphorylation of the newly identified phosphoresidues in NICD and the factors and mechanism responsible. 

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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