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CARD14 regulation of NF-kB activation in psoriasis


Project Description

Project Details:

We invite applications for a Department of Medicine-funded PhD studentship to investigate the function of CARD14 in skin inflammation in the laboratory of Professor Steve Ley ().

Rare inherited and de novo mutations in Card14 promote development of psoriasis, a chronic inflammatory skin disease (1, 2). Genome wide association studies also indicate a role for Card14 in common psoriasis, which affects 2-3% of adults in the UK (1, 3).

We have shown that psoriasis-associated Card14 mutations induce the constitutive formation of a CARD14/BCL10/MALT1 complex, triggering BCL10 and MALT1 dependent activation of NF-κB and expression of pro-inflammatory genes in the absence of an inflammatory signal (4).

The aim of this project is to investigate how CARD14 induces skin inflammation and the role of CARD14 in immune responses to pathogens at epithelial cell barriers. This work will be done in collaboration with Dr. Jessica Strid (Imperial College London) and involves use novel genetic models that enable CARD14 signalling to be switched on or off in specific cell types.

This project will significantly increase our understanding of the functions of the CARD14/NF-kB signalling pathway in inflammation and immune responses. This may lead to novel, more targeted approaches to treat psoriasis, a serious autoimmune disease that has substantial negative impacts on both physical and emotional aspects of patient quality of life.

More information on research by the Ley laboratory can be found here: http://www.imperial.ac.uk/people/s.ley

Requirements:

Applicants must have/or expect to gain a first class or upper second class honours degree or Overseas equivalent in a relevant subject area (biochemistry and immunology) preferably with experience with in vivo immunology assays and models. A Master’s Degree is preferable but not essential. We look for highly motivated applicants with excellent interpersonal, written and oral communication skills.

How to Apply:

Applicants are requested to send a full CV (including the names and email addresses of at least two academic referees), and personal statement (detailing why you are interested in the research project). Suitable candidates will be then asked to complete an electronic application form at Imperial College London in order for their qualifications to be addressed by College Registry.

Please submit your application to Lisa Quinn ().

Funding Notes

Stipend: £18,000 (inclusive of London allowance) per annum + Tuition Fees (Home/EU rate) for 3 years.

A tax-free stipend and home UK/EU fees for 3 years will be awarded. Overseas students should be able to demonstrate adequate financial support to cover the difference between the home/EU fee and the overseas fee. Applicants are also required to meet Imperial College’s English language requirements. Please see the following link: View Website

References

1. Jordan CT, et al. (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-κB, in psoriasis. Am. J. Hum. Genet. 90:796 - 808.
2. Jordan CT, et al. (2012) PSORS2 is due to mutations in CARD14. Am. J. Hum. Genet. 90:784 - 795.
3. Tsoi LC, et al. (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genetics. 44:1341 - 1348.
4. Howes A, et al. (2016) Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation. Biochem. J. 473:1759 - 1768.

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