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The role of SORL1 in B cell antigen trafficking


Project Description

B cells are a crucial element of adaptive immunity by producing antibodies to neutralise invading pathogens. For an effective antibody response, a B cell must interact with and internalise (endocytose) antigens through its surface B cell receptor. Antigen is processed and presented to T cells, which provide survival and differentiation signals. Understanding endocytosis would allow us to design antigens that promote acquisition and presentation by B cells, with direct implications for vaccine design.
To do this, we have performed a whole-genome CRISPR/Cas9 screen and identified novel genes regulating antigen endocytosis. One of these is SORL1, a sorting receptor with protein trafficking functions.
In the brain, SORL1 mutations, cause altered trafficking of amyloid precursor protein and are a major risk factor for Alzheimer disease. SORL1 defects have also been linked to abnormal ion balance, HER2 trafficking in cancer, atherosclerosis and obesity.
Its role in B cells is unknown and this project aims to confirm the screen results in B cells lines, image SORL1 localisation in the context of B cell activation and investigate how SORL1 mutation affects B cell development, antigen presentation and germinal centre responses. The project likely involves flow cytometry, fluorescence microscopy and molecular biology, including CRISPR. It would suit candidates interested in immunology, cell biology and genetic engineering.

ENTRY REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language

Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.

The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
• IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
• TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
• A valid Certificate of Proficiency in English grade A or B;
• A valid Certificate of Advanced English grade A; or
• A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.

For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English

INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/

Funding Notes

*FUNDING CONFIRMED – Department for the Economy (DfE) Award*

Eligibility for both fees (£4,327 for 2019/20, 2020/21 TBC) and maintenance (£15,009 for 2019/20, 2020/21 TBC) depends on the applicants being either an ordinary UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding the start of the studentship.

Non UK residents who hold EU residency may also apply but if successful may receive fees only.

For further details re eligibility criteria (including academic, citizenship and residency criteria) please click on the following link: View Website

References

Please visit the School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, website for further details about the Centre:

http://www.qub.ac.uk/research-centres/CEM/

When applying, please choose 'MEDICINE' as your subject area/School.

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