(MRC DTP) Understanding the role of inositol lipids in immune receptor dynamics and signaling

B lymphocytes play a crucial role in adaptive immunity, being responsible for antibody production as well as contributing to antigen presentation and cytokine secretion to coordinate the immune response. Stimulation of B-cells occurs primarily through the B-cell receptor (BCR), a surface-exposed membrane-integrated immunoglobulin. Antigen binding to the BCR stimulates a number of downstream signaling pathways that control B-cell differentiation, proliferation and migration. Dysregulation of BCR signaling is responsible for human malignancies such as lymphoid leukaemia and lymphoma, and is also associated with various immunological disorders. Because of its crucial importance in B-cell physiology, the BCR has been intensively investigated for many years. In our recent unpublished work, we have uncovered a new role for inositol lipids in the dynamics and signaling of the BCR. Gene editing of inositol phosphatases in B-cells has revealed that these enzymes, and their lipid substrates, play a previously unknown but crucial intermediary step in BCR activation. The goal of this project is to decipher the mechanisms by which the inositol phosphatases control BCR mobility, trafficking and signaling, and then to determine the importance of this regulation in B-cell physiology, looking at the differentiation, growth and migration of B-cells. A combination of cell biology and immunological approaches will be used to this end, which will include a significant amount of high-end live and fixed cell imaging. The findings will provide major new insights into the BCR and will have significant implications for our understanding of the healthy immune system and B-cell disorders such as leukaemia and lymphoma.

http://www.manchester.ac.uk/research/martin.p.lowe/
https://www.research.manchester.ac.uk/portal/madhvi.menon.html

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships