Studentship | How do dead kinases regulate immune signalling?

MRC Funded
Project with

The Kulathu lab is interested in understanding the molecular mechanisms of how posttranslational modifications mediate signal transduction. The innate immune response is the first line of defence against bacteria, viruses and parasites. When innate immune receptors are triggered it leads to the formation of a large oligomeric signalling complex called the Myddosome. Within the Myddosome, the IRAK kinases are activated to trigger a signalling cascade that culminates in the expression and secretion of cytokines that shape the immune response to invading pathogens. There are 4 IRAK kinases expressed in humans, two of which (IRAK2 and IRAK3) lack key catalytic residues and are therefore dead kinases or pseudo-kinases. The aim of this project will be to understand the molecular mechanisms by which these dead kinases regulate immune signalling. This project will build on recently published work (see Lange et al, Structure 2020), this project will utilize protein biochemistry, cryo-electron microscopy, X-ray crystallography to define how IRAK kinases are activated and regulated. This project has the potential to reveal fundamental principles underlying the activation and regulation of innate immune signalling, and reveal how they could be modulated to treat inflammatory diseases such as arthritis, artherosclerosis, systemic lupus erythematosus and psoriasis.

 

References:

  1. Lange et al. Structure 2020. DOI: https://doi.org/10.1016/j.str.2020.11.004
  2. Gay N et al. Nature Rev Immunol. DOI: https://doi.org/10.1038/nri3713  

 

At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.

 

Please send a CV with contact details of three referees to and a cover letter, explaining why you have chosen to apply to MRC PPU, to mrcppu-phd-admin@dundee.ac.uk. The closing date for applications is 15th November 2021. We will chat with long-listed applicants by Zoom in November/December 2021 to select candidates to take forward. Interviews will take place in January 2022. Applications from overseas students are welcome.

Application Procedure

Should you wish to apply for the above PhD position, please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply:

mrcppu-phd-admin@dundee.ac.uk