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Deciphering the metabolic regulation of inflammasome activation

  • Full or part time
  • Application Deadline
    Tuesday, April 30, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

A 3-year Department of Medicine PhD studentship is available to work in the laboratory of Dr Paras Anand, in the Section of Infectious Diseases and Immunity at Imperial College London. The successful applicant will be joining an internationally-renowned Department, within one of the world’s top research universities. We are seeking a highly motivated and enthusiastic candidate with background in immunology/ microbiology/ biochemistry and a strong interest in innate immunity.

The laboratory of Dr. Paras Anand is broadly interested in investigating the roles of innate immune receptors, mainly the NLRs and inflammasomes, during infectious and ‘sterile’ stimuli. The NLRP3 inflammasome, in particular, is recognized to play critical roles in infectious, inflammatory, and autoimmune diseases and can be activated by diverse stimuli. Our recent studies suggested cellular cholesterol transport as a key homeostatic mechanism regulating the NLRP3 inflammasome thereby highlighting a new perspective on the metabolic control of inflammasome (Journal of Cell Biology, 2018). Specifically, we demonstrated that the blockade of cholesterol lysosomal efflux pathway dampens NLRP3 inflammasome activation. Moreover, we established that cholesterol transport to the ER is required for the activation of the NLRP3 inflammasome. Thus, molecular pathways that mediate intracellular sterol transport impact inflammasome activity and may be exploited for translational purposes. This exciting PhD position will investigate the detailed roles of cholesterol transport pathways in inflammasome activation. We will characterize how cholesterol homeostasis influences inflammasome activity and cellular metabolism, and whether these pathways might affect immunity to pathogens and the inflammatory response. This work will be done in collaboration with Dr. Jacques Behmoaras (Imperial College London). For further information, please find our previously reported findings from the reference section below.

Training
The selected candidate will extensively use immunology, microbiology, molecular biology, biochemistry and imaging to address the above questions. In addition, the candidate will be exposed to state-of-the-art facilities including core laboratories for proteomics, microarrays, and animal facilities. Imperial College London is among the top 10 universities in the World and has an established PhD programme. The university provides support with high-quality training and career development activities which includes development of skills essential for career progression such as presentation and writing skills. The student will be based in the Section of Infectious Diseases and Immunity at the Hammersmith Hospital Campus of Imperial College London, which provides an exciting training environment.

To apply, please send your CV (with contact details of 2 academic referees), and a research statement (max. 1.5 pages) describing why you are suitable for this PhD studentship to Ms. Emily Wood () by 30 April 2019. Informal enquires can be sent to Dr. Paras Anand (). Please note that only shortlisted candidates will be contacted for interviews which are tentatively scheduled in the third week after the application deadline.

Funding Notes

Candidates must have a first class or upper second-class Honours degree (or overseas equivalent) in a relevant subject area. A Master’s Degree is desirable but not essential.
The 3-year studentship covers tuition fees and provides a tax-free stipend of £18,000 per annum. 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. de la Roche M, Hamilton C, Mortensen R, Jeyaprakash AA, Ghosh S, Anand PK. Trafficking of cholesterol to the ER is required for NLRP3 inflammasome activation. J Cell Biol. 2018 Oct 1;217(10):3560-3576.
2. Hamilton C, Tan L, Miethke T, Anand PK. Immunity to uropathogens: the emerging roles of inflammasomes. Nat Rev Urol. 2017 May;14(5):284-295.
3. Lupfer C*, Anand P* et al., Reactive oxygen species regulate Caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection. PLoS Pathogens 2014; 10:e1004410.
4. Lupfer C, Thomas P, Anand P et al., Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nature Immunology 2013; 14:480-488.
5. Anand P et al., NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 2012; 488:389-393.

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