Type 1 diabetes; novel insights from analysis of single B cells at Cardiff University on FindAPhD.com

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Prof C Dayan, Dr S Richardson, Dr K Gillespie, Dr Danijela Tatovic No more applications being accepted Competition Funded PhD Project (UK Students Only)

Cardiff United Kingdom

About the Project

B cells play a key role in type 1 diabetes (T1D). Using cutting edge imaging, single cell and NanoString technologies, human B cells from
pancreas, lymph node and skin samples from patients will be interrogated and isolated, their transcriptome analysed and their immunoglobulin heavy and light chains expressed to allow autoantibody analysis at the single cell level for the first time.

Recent studies have demonstrated that B lymphocytes play a key role in type 1 diabetes (T1D). Studies from our group have shown that islet autoantibodies, derived from B cells, can be used to predict over 90% of the children who will go on to develop T1D. Recently we have shown that the presence of B cells in the pancreatic islets is associated with disease onset earlier in childhood. Until now, it was only possible to study autoantibodies in serum without being able to separate individual immunoglobulin molecules and only a limited number of characteristics of individual B cells could be studied. Recent developments in state-ofthe-art multiplex immunofluorescence imaging and analysis (using the Vectra® Polaris™ Automated Quantitative Pathology Imaging System), and single cell “bar coding” and analysis (using NanoString and 10x technology) will allow a deeper interrogation of B cells in human T1D pancreatic tissue and whole transcriptome data from single cells to be determined.
Assay platforms have become available to sequence both the heavy and light chains of individual B cells. Our group developed techniques to isolate antigen specific B cells and we also have access to precious material from human pancreases and lymph nodes from subjects with T1D as well as skin from sites of islet specific antigen immunisation. In this project, B cells from these sites will be isolated or obtained by laser-capture microscopy and bar coded for single cell transcriptomic analysis and B cell receptor (immunoglobulin) sequencing. The heavy and light chains will then be co-expressed to generate secreted monoclonal antibodies whose specificity can be determined in established in-house assays. The project will generate some of the first human monoclonal antibodies to islet-antigens for detailed analysis, provide a whole transcriptomic profile of confirmed antigen-specific B cells and allow the detailed in situ analysis of B cells in rare T1D donor pancreas. These new technologies will provide key information on the role of B cells in T1D pathogenesis, inform prediction strategies and identify B cell subsets that can be targeted for immunotherapy.

Funding Notes

A GW4 BioMed MRC DTP studentship includes full tuition fees at the UK/Home rate, a stipend at the minimum UKRI rate, a Research & Training Support Grant (RTSG) valued between £2-5k per year and £300 annual travel and conference grant based on a 3.5-year, full-time studentship.
These funding arrangements will be adjusted pro-rata for part-time studentships. Throughout the duration of the studentship, there will be opportunities to apply to the Flexible Funding Supplement for additional support to engage in high-cost training opportunities.

References

ELIGIBILITY

International and EU students are eligible to apply for these studentships but should note that they may have to pay the difference between the home UKRI fee ( https://www.ukri.org/skills/funding-for-research-training/ ) and the institutional International student fee ( https://www.cardiff.ac.uk/__data/assets/pdf_file/0008/1735154/Fees-Template-PGR-International-2020-21-Version-1-04.12.2019.pdf ). We will update applicants when further information becomes available.

ENTRY REQUIREMENTS

Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject. 
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS) 

In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences. Further training can be provided to assist with discipline conversion for students from non-medical backgrounds.

HOW TO APPLY

Stage 1: Applying to the DTP for an Offer of Funding
Please follow the instructions at the following link to apply to the DTP.
https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl-2

Stage 2: Applying to the lead institution for an Offer of Study

This studentship has a start date of October 2021. In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the application system, click the 'Visit Institution' button on this advert) 
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2021). This will take you to the application portal. 
In order to be considered candidates must submit the following information: 

• Supporting statement 
• CV 
• Qualification certificates 
• Proof of English language (if applicable)
• In the research proposal section of the application, please specify the project title and supervisors of the project and copy the project description in the text box provided. In the funding section, select “I will be applying for a scholarship/grant” and specify advertised funding from GW4 BioMed MRC DTP. If you are applying for more than one Cardiff University project, please note this in the research proposal section as the form only allows you to enter one title.

Where will I study?

Cardiff University

At the heart of our vibrant research culture is a welcoming community of students and staff, who share a single ambition: to tackle the grand challenges of our time and make a positive impact around the world.

Type 1 diabetes; novel insights from analysis of single B cells

Cardiff University Cardiff School of Medicine