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MSc by Research: How do CDKs phosphorylate the right substrates at the right time?


   School of Life Sciences

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  Dr T Ly  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Cell division is crucial for tissue renewal, wound repair, and the immune response. Cancer occurs when mechanisms that regulate cell division go wrong. The cell division cycle is controlled by the ordered phosphorylation of substrates by cyclin-dependent kinase (CDK) complexes. In yeast a single CDK can drive cell cycle progression, but in animal cells several different CDK complexes drive different stages of the cell cycle. How different CDK complexes target the right substrates is poorly understood. This project will use a combination of biochemistry, genetics, structural biology, and cell biology to understand the mechanistic basis for temporal ordering of CDK substrate phosphorylation in human cells, and thus contribute to answering a key open question in the field.  

The Ly group has applied state of the art phosphoproteomics to dissect how non-catalytic subunits of CDKs contribute to substrate choice. The student will develop and apply novel kinase assays in which protein phosphorylation is induced in fixed and permeabilized human cells using recombinant CDK complexes. Global cellular phosphorylation levels are then measured using quantitative mass spectrometry. The kinase assay will allow the student to assess how substrate phosphorylation and substrate choice is affected by qualitative factors (i.e., the composition of the CDK complex) versus quantitative factors (i.e., concentration and kinetics). Our preliminary data on CDK1 surprisingly show that non-catalytic subunits of CDK1 can promote phosphorylation of non-proline directed phosphoacceptor sites, revealing a secondary consensus sequence specific to the non-catalytic subunit. These results suggest that contrary to textbook models, CDK1 can phosphorylate many non-proline directed sites in the human proteome. However, the function of these non-proline directed sites is unknown. This project will explore the function of these non-canonical sites and investigate substrate phosphorylation by other CDKs, including CDK2 and CDK4/6.  

 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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