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Deciphering the metabolic regulation of inflammasome activation


Department of Infectious Disease

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Dr P Anand No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

A 3-year PhD studentship is available to work in the laboratory of Dr Paras Anand, in the Department of Infectious Disease at Imperial College London. The successful applicant will be joining an internationally renowned Department, within one of the world’s top research universities.

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. Recent results from the lab 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. This exciting PhD position will investigate the detailed roles of metabolic pathways in inflammasome activation. We will characterize how lipid metabolism influences inflammasome activity, and whether these pathways might affect immunity to pathogens and the inflammatory response. This work will be carried out in collaboration with Dr.Jacques Behmoaras (Imperial College London).

The selected candidate will extensively use immunology, biochemistry, molecular biology, and microbiology 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. 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 Adult Infectious Disease at the Hammersmith Hospital Campus of Imperial College London, which provides an exciting training environment.


How to Apply
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 as a single PDF file, to Ms. Emily Wood ([Email Address Removed]) by 14th December 2020. Please name your PDF file as (FirstName_LastName_PhDApp). Informal enquires can be sent to Dr Paras Anand ([Email Address Removed]). Please note that only shortlisted candidates will be contacted for interviews.

Eligibility
We are seeking a highly motivated and enthusiastic candidate with background in immunology / biochemistry and a strong interest in innate immunity. Prior experience in metabolism is desirable.

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.

Funding Notes

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:
http://www.imperial.ac.uk/study/pg/apply/requirements/english.

References

1. Anand, PK. Lipids, inflammasomes, metabolism, and disease. Immunol Rev 2020 Sep;297(1):108-122.
2. Hamilton C, Anand PK. Right place, right time: localisation and assembly of the NLRP3 inflammasome. F1000Res. 2019 May 17;8:F1000 Faculty Rev-676.
3. 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.
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