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MSc by Research: Regulation of the stability of the Notch intracellular domain in iPS derived presomitic mesoderm cells


   School of Life Sciences

  Prof J K Dale  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Notch is one of the major highly conserved signalling pathways that regulate cell-cell communication which involves gene regulation mechanisms that control multiple processes during development and adult life. Upon extracellular ligand binding, Notch transmembrane receptors are cleaved, releasing the intracellular domain (NICD) that translocates to the nucleus to regulate expression of specific developmental gene cohorts. NICD is highly labile, and phosphorylation-dependent turnover acts to restrict Notch signalling. Most canonical Notch activity relies on this regulation of NICD turnover. Moreover, aberrant NICD turnover contributes to numerous cancers and diseases. The stability of NICD and therefore duration of the Notch signal is regulated by phosphorylation of the C-Terminal PEST domain which leads to subsequent recruitment of FBXW7, F-Box and WD Repeat Domain Containing 7, (a key component of the SCFSel10/FBXW7 E3 ubiquitin ligase complex). Ultimately, this results in ubiquitylation and proteasomal degradation of NICD. The main aim of this project is to decipher the role different kinases play that phosphorylate NICD and target it for degradation. 

One of the key processes the Notch pathway regulates during embryonic development is the timing of the periodic formation of segments from the unsegmented presomitic mesoderm. These segments will give rise to a number of derivatives one of which is the bones and associated muscles of the skeleton. The timing of this process is regulated by dynamic oscillatory expression of “clock genes” which is regulated by dynamic Notch signalling. NICD is particularly unstable in presomitic mesoderm cells and modifying this stability changes the pace of segment formation. This project will be using iPS cells differentiated into presomitic mesoderm cells in vitro, to identify the kinases that are responsible for this reduced NICD stability. 

Please see our website for further details on the programme:

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

Please note before submitting your application that you must list your top three project choices in the Research Proposal section of the application form.

You apply for this course using our Direct Application System. Once you've signed up for an account you'll be asked to search for a course.

https://www.dundee.ac.uk/study/pgr/research-areas/life-sciences/

To find Life Science MSc by Research you should select the following options:

·   Course type: Research Postgraduate

·   Keyword: Life

When you complete your form, you should include your top 3 project choices, 2 letters of reference, uploaded under "Other Information" > "Supporting documents" and a personal statement. Failure to do so will delay your application.

Please note when submitting an application that we have the following deadline dates throughout the year:

September Starts - Application Deadline 1st May, Interview Date - Late June

January Starts - Application Deadline 1st Sep, Interview Date - Late October

May Starts - Application Deadline 1st Feb, Interview Date Late March

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