Project Title: Deep immuno-profiline of Aspergillus bronchitis and allergic bronchopulmonary aspergillosis in cystic fibrosis

 

Project Description

Applications are invited for a fully-funded 3-year PhD studentship. This studentship is integral to a major Cystic Fibrosis Trust Strategic Research Centre in Fungal Immunotherapy (TrIFIC) made to Imperial College London collaborating with University of Manchester and University of Exeter. The overall aim of the SRC is to systematically define the underlying mechanisms of inflammation in pulmonary aspergillosis in the context of cystic fibrosis. This will allow enable development of immuno-diagnostic tests to identify which patients will benefit from targeted immunotherapies that can be repurposed in CF. The project will provide the successful applicant with stat-of-the-art training in the latest human immunophenotyping approaches at the interface of respiratory infection and allergy.

We are seeking a highly motivated student to join the opportunistic pathogens group led by Dr Darius Armstrong-James within the MRC Centre for Molecular Bacteriology and Infection (CMBI) within the Faculty of Medicine of Imperial College London at the South Kensington Campus in collaboration with Dr Mo Shamji in the National Heart and Lung Institute (NHLI).

The aim of the project is to undertake deep immune-profiling of the host response to the major mould pathogen Aspergillus fumigatus in patients with allergic bronchopulmonary aspergillosis and Aspergillus bronchitis. This will allow us to identify those individuals who will have poor outcomes from infection and develop novel targeted immuno-therapeutic approaches for fungal disease. The outstanding supervisory panel will allow the student the opportunity to be exposed to a range of cutting-edge immune-profiling techniques for human disease pathogenesis and translational immunotherapy including spectral cytometry, single-cell RNAseq, metagenomics and proteomics. 

Contacts:
Dr Darius Armstrong-James (
http://www.imperial.ac.uk/people/d.armstrong)
Dr Mo Shamji (https://www.imperial.ac.uk/people/m.shamji99) 

 

How to apply
To apply: please send a single PDF document including a one-page cover letter discussing research interest and experiences, a two-page CV, a copy of transcripts, and contact information for two references to Dr Armstrong-James (d.armstrong@imperial.ac.uk) with subject line “CF_PhD_App” before the closing date of 14 November 2021.

The successful candidate must be able to start the project by early January 2022.

Funding & Eligibility 
The studentship is open to UK and EU nationals eligible for Home fees. It includes payment of Home fees and an annual stipend starting at £22,278 for 3 years.

Applicants must have a first or upper second-class BSc degree from a UK University, or the overseas equivalent, in a relevant area of immunology, biochemistry, chemistry or microbiology. Experience in immunology and bioinformatics is a major advantage. Applicants must also meet Imperial College’s English language requirements.

 

References

  1. CFTR Modulators Dampen Aspergillus-Induced Reactive Oxygen Species Production by Cystic Fibrosis Phagocytes. Currie AJ, Main ET, Wilson HM, Armstrong-James D, Warris A. Front Cell Infect Microbiol. 2020 Jul 24;10:372. doi: 10.3389/fcimb.2020.00372.
  2. Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is ssociated with clinical response. Golebski K, Layhadi JA, Sahiner U, Steveling-Klein EH, Lenormand MM, Li RCY, Bal SM, Heesters BA, Vilà-Nadal G, Hunewald O, Montamat G, He FQ, Ollert M, Fedina O, Lao-Araya M, Vijverberg SJH, Maitland-van der Zee AH, van Drunen CM, Fokkens WJ, Durham SR, Spits H, Shamji MH.Immunity. 2021 Feb 9;54(2):291-307.e7. doi: 10.1016/j.immuni.2020.12.013. Epub 2021 Jan 14.PMID: 33450188
    1. Human NK Cells Develop an Exhaustion Phenotype During Polar Degranulation at the Aspergillus fumigatus Hyphal Synapse. Santiago V, Rezvani K, Sekine T, Stebbing J, Kelleher P, Armstrong-James D. Front Immunol. 2018 Oct 22;9:2344. doi: 10.3389/fimmu.2018.02344. eCollection 2018.
    2. Ibrutinib blocks Btk-dependent NF-kB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis. Bercusson A, Shah A, Warris A, Armstrong-James D, Blood. 2018 Jul 18. pii: blood-2017-12-823393. doi: 10.1182/blood-2017-12-823393. [Epub ahead of print] 
    3. Armstrong-James D, Brown GD, Netea MG, Zelante T, Gresnigt MS, van de Veerdonk FL, Levitz SM. Immunotherapeutic approaches to treatment of fungal diseases. Lancet Infect Dis. 2017 Dec;17(12):e393-e402. doi: 10.1016/S1473-3099(17)30442-5. Epub 2017 Jul 31. Review. PubMed PMID: 28774700.
    4. Shah A, Kannambath S, Herbst S, Rogers A, Soresi S, Carby M, Reed A, Mostowy  S, Fisher MC, Shaunak S, Armstrong-James DP. Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death. Am J Respir Crit  Care Med. 2016 Nov 1;194(9):1127-1139. PubMed PMID: 27163634; PubMed Central PMCID: PMC5114448.
    5. Herbst S, Shah A, Mazon Moya M, Marzola V, Jensen B, Reed A, Birrell MA, Saijo S, Mostowy S, Shaunak S, Armstrong-James D. Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus. EMBO Mol Med. 2015 Mar;7(3):240-58. doi: 10.15252/emmm.201404556. PubMed PMID: 25637383; PubMed Central PMCID: PMC4364943.