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PhD Studentship: NIHR Newcastle Biomedical Research Centre (BRC) – Fat, Fibroblasts and Immunotherapy Resistance in NASH-HCC

Newcastle University

Qualification Type: PhD
Location: Newcastle upon Tyne
Funding for: UK Students, EU Students, International Students
Funding amount: 100% home tuition fees and an annual stipend of £18,622 (2023/2024 UKRI rate). International candidates will be required to fund the difference between the home and international fees
Hours: Full Time
Placed On: 1st February 2024
Closes: 15th March 2024
Reference: TC086

Award Summary

100% home tuition fees and an annual stipend of £18,622 (2023/ 2024 UKRI rate). International candidates will be required to fund the difference between the home and international fees. 

Overview

This studentship will computationally investigate the heterogeneity of CAFs in NASH-HCC patients, employing bioinformatics and AI led image analysis of single-cell and spatial datasets, identifying features of disease stage, progression and therapeutic response. 

Objective 1: Profile cancer-associated fibroblast heterogeneity in patients with NASH-HCC. 

Bioinformatics analysis of pre-existing scRNA-seq data from matched tumour and non-tumour biopsy tissue in 8 NASH-HCC. The student will learn to perform quality control, normalisation, dimensionality reduction, clustering, differential gene expression and trajectory analysis of scRNAseq data. The student will correlate the identified CAF cluster signatures with those that predict immunotherapy response.

Objective 2: Develop new AI technologies to analyse multiplexed spatial imaging data of NASH-HCC patient tumours. 

The student will analyse the first spatially resolved multiplexed analysis of NASH-HCC immunotherapy responders and non-responders, performing imaging mass cytometry analysis using standard published workflows. The student will work to develop advanced AI tools for image analysis, centred on detailed spatial relationships and specific cell-cell interactions, potentially limiting immunotherapy responses. 

Objective 3: Perform an integrated analysis to identify serum signatures associated with CAF heterogeneity, tumour stage, progression, and response to therapy. 

The connection between tumour stroma composition and immune cell presence and over 4000 circulating serum markers (O-link assays) will be explored, pinpointing serum signatures indicative of disease stage, progression, and treatment response.

Methodology and skills gained 

The student will develop computational analysis skills, analysing and integrating large bulk RNAseq and scRNAseq datasets and highly multiplexed imaging data, also learning the fundamentals of machine learning AI analysis. They will be immersed in a thriving laboratory environment, with the opportunity to develop wet lab skills alongside their predominantly computational research. 

Number Of Awards: 1

Start Date: September 2024 

Award Duration: 36 months 

Application Closing Date: 15 March 2024 

Sponsor: NIHR Newcastle BRC 

Supervisors

Dr Jack Leslie 

Professor Helen Reeves 

Dr Jérémie Nsengimana 

Eligibility Criteria

You must have or be expected to gain a minimum 2:1 Honours degree or international equivalent in a subject relevant to the proposed PhD project. A master’s qualification will be advantageous. 

Applicants whose first language is not English require an IELTS score of 6.5 with a minimum of 5.5 in each subsection. International applicants may require an ATAS clearance certificate prior to obtaining their visa and to study on this programme. 

How To Apply

You must apply through the University’s Apply to Newcastle Portal 

In ‘Course choice’ tab, put ‘Postgraduate Research’ in 'Type of Study', ‘Full Time’ in ‘Mode of Study’, ‘2024’ in ‘Year of Entry’, code ‘8440F’ in ‘Course Title’, blank in ‘Research Area’. Press ‘Search’, select ‘PhD Translational and Clinical Research (FT)’, and save selection. 

Either upload a document or write into ‘Personal Statement’. Put code ‘TC086’ in ‘Studentship/Partnership Reference’. When prompted for research proposal, select ‘Write Proposal’. Type in the title of the research project from this advert. A research proposal is not required. Please upload a covering letter, CV and state how your interests and experience relate to the project.  

Degree transcripts/certificates and, if English is not your first language, a copy of your English language qualification if completed must be uploaded.  

Contact Details

jack.leslie@newcastle.ac.uk 

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