University College London Featured PhD Programmes
Engineering and Physical Sciences Research Council Featured PhD Programmes
University of Sheffield Featured PhD Programmes
Sheffield Hallam University Featured PhD Programmes
European Molecular Biology Laboratory (Heidelberg) Featured PhD Programmes

The contribution of human mast cells to innate functional memory in anti-bacterial responses


Project Description

In the recent years, it has become evident that after infection or vaccination innate immune cells have the capacity to adapt and modify the nature of their activities following a single immunostimulatory challenge and display a long-term functional memory. A phenomenon that has been defined as ‘trained innate immunity’.

Mast cells (MCs) are tissue resident cells that are strategically located in mucosal tissues and are among the first cells to come in to contact with pathogens. MCs contribute to bacterial immunity through the release of a great variety of pro- and anti-inflammatory pre-stored and de novo synthesized mediators that lead to the recruitment of immune cells to the site of infection and modulation of their activities and direct bacterial killing.

Whether MCs are trained upon single microbial immunomodulatory challenges, whether this training leads to a temporal distant functional memory and how this influences protection against multiple diseases remains unclear. The goal of the project is to investigate the contribution of human mast cells to innate functional memory. In more detail, aims of the study are to investigate which microbial immunomodulatory stimuli induce memory MCs, what is the phenotype and effector functions of a trained MC and how does MC memory translate to disease protection.

This project involves include culturing and differentiation of human MCs and the evaluation of their function by flow cytometry (e.g. CyTOF), advanced immunofluorescence, transcriptomic analysis and bioinformatics analysis, bacterial culture and infection assays. Moreover, this project will be combining MC-centred immunology research and microbiological expertises at the internationally recognized Manchester Collaborative Centre of Inflammation Research and Lydia Becker Institute of Immunology and Inflammation.

Training/techniques to be provided:
Methodologically, the project will include the culture and differentiation of human mast cells and other cell lines and the evaluation of their function by state-of-the-art flow cytometry, advanced immunofluorescence, transcriptomic analysis, deep immunophenotyping and metabolic/proteomic approaches.

Entry Requirements:
Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in life sciences. A Master degree in a relevant subject and experience in cell biology/ immunology is desirable.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

• Garcia-Rodriguez KM, Goenka A, Alonso-Rasgado MT, Hernández-Pando R, Bulfone-Paus S. The Role of Mast Cells in Tuberculosis: Orchestrating Innate Immune Crosstalk? Front Immunol. 2017 Oct 17;8:1290. doi: 10.3389/fimmu.2017.01290.
• Bulfone-Paus S, Nilsson G, Draber P, Blank U, Levi-Schaffer F. 2017.Positive and Negative Signals in Mast Cell Activation. Trends Immunol. doi: 10.1016/j.it.2017.01.008.
• Corbett D, Goldrick M, Fernandes VE, Davidge K, Poole RK, Andrew PW, Cavet J, Roberts IS. Listeria monocytogenes has both a bd-type and an aa3 -type terminal oxidase which allow growth in different oxygen levels and both are important in infection. Infect Immun. 2017 Aug 14. pii: IAI.00354-17. doi: 10.1128/IAI.00354-17.
• Bahri R, Custovic A, Korosec P, Tsoumani M, Barron M, Wu J, Sayers R, Weimann A, Ruiz-Garcia M, Patel N, Robb A, Shamji M.H., Fontanella S, Silar M, Mills C, Simpson A, Turner P.J. and Bulfone-Paus S. 2018. Mast cell activation test in the diagnosis of allergic disease and anaphylaxis. J Allergy Clin Immunol. pii: S0091-6749(18)30308-7.
• Jadkauskaite L, Bahri R, Farjo N, Farjo B, Jenkins G, Bhogal R, Haslam I, Bulfone-Paus S, Paus R. Nuclear factor (erythroid-derived 2)-like-2 pathway modulates substance P-induced human mast cell activation and degranulation in the hair follicle. J Allergy Clin Immunol. 2018 May 31. pii: S0091-6749(18)30777-2. doi: 10.1016/j.jaci.2018.04.039.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2019
All rights reserved.