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Understanding the mechanism of membrane insertion and inhibition of channels and pore forming proteins

Annual stipend equalling the full UK Research Council rate of £15,009 (rate for 2019/20), plus tuition fees covered at the rate for UK/EU students.

Proteins of the CLIC family and MLKL have the striking feature of being able to insert in and permeabilise the plasma membrane through the formation of channels or pores, respectively. These proteins are important targets in the treatment of different types of cancer, heart stroke, inflammation and viral replication, and new drugs targeting them are currently in clinical studies. However, little is known about their activation mechanism, the membrane insertion process, the structural details of the membrane bound forms and their inhibition.

The goal of this project is to study the membrane insertion and inhibition mechanisms of CLIC1, CLIC4 and MLKL. We aim to use an integrative structural biology approach, combining solution NMR, solid state NMR, X-Ray Crystallography, Neutron Reflectivity, and fluorescence microscopy (both at the cellular and single molecule level) to fully understand the membrane insertion of these proteins with different levels of spatial and temporal resolution. These will allow us to understand the function and inhibition of the different forms of these proteins.

Criteria

UK residency applies
UK or EU applicant who has resided or studied in the UK for 3 years prior to the start of the course.
Overseas national who has been ordinarily resident (i.e. not for study purposes) in the UK for 3 years prior to the start of the course and has indefinite leave to remain in the UK.

Open eligibility
Overseas applicants may apply but must be in a position to fund the difference between home and international fees.


How to apply

Informal enquiries can be addressed to: Dr Jose L. Ortega-Roldan  (J.L.Ortega-Roldan@kent.ac.uk)


Applications can be made using the online University application page where the project title should be entered as the proposed area of research and Dr Jose L. Ortega-Roldan as supervisor. Please include a CV and a cover letter. Applications must be received by 23 April 2019.


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