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(MRC DTP) The contribution of human mast cells in multi-allergen dominated allergic responses

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  • Full or part time
    Prof S Bulfone-Paus
    Dr A Simpson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Allergic diseases, such as asthma, allergic rhinitis, and food allergy, are an important public health burden and seriously affect the quality of life of people, particularly in developed countries. These conditions are characterised by the presence of IgE antibodies to common things in our environment, such as house dust mite (asthma), pollen (allergic rhinitis), and peanut ( food allergy). The routes of allergens intake and the frequency are highly variable. For example grass pollen exposure is seasonal while food allergens are taken up accidentally and through the gastrointestinal tract. The symptoms associated with the latter are more systemic and severe compare to the inhalant allergen. Mast cells, together with basophils, are the main effector cells in IgE-mediated allergic reactions. During the allergic response, mast cells upon allergen encounter are activated and subsequently release rapidly their granular content, including histamine, cytokines, chemokines, proteases, and lipid mediators.

Furthermore, the cytokine IL-33, produced by damaged epithelial cells contributes to acute allergic reactions by enhancing the IgE-mediated activation of mast cells. For patients allergic to multiple allergens, knowing which allergen or combinations of allergens are driving the symptoms is clinically relevant and as of yet is a poorly understood area. Furthermore, it remains unclear how allergen re-exposure, as well as combinations of unrelated allergens, affect mast cell activities. Therefore, the goal of the project is to gain a better understanding of the role of human mast cells in complex multi-allergen dominated allergic responses.

This project involves culturing and differentiation of human mast cells and the evaluation of their function by flow cytometry (e.g. CyTOF), advanced immunofluorescence, transcriptomic analysis and bioinformatics analysis. Moreover, this project will be combining mast cell-centred immunology research and allergy clinical expertise at the internationally recognised Manchester Collaborative Centre of Inflammation Research and Lydia Becker Institute of Immunology and Inflammation.

www.mccir.manchester.ac.uk/research/areas/homeostasis-pathogenesis/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

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.



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