Faculty of Biology, Medicine and Health

The University of Manchester

  (MCRC Non-clinical) Dissecting different T cell death signatures in oesophagogastric adenocarcinoma to discover new cancer immune-evasion strategies

  , Dr Florent Mouliere, , , ,  Friday, November 15, 2024  Competition Funded PhD Project (Students Worldwide)

About the Project

Oesophago-gastric adenocarcinomas (OGA) are cancers of unmet need of particular relevance in North West England. Checkpoint inhibitors are the most effective drugs to prolong OGA patient survival, but responses are lower than in similarly mutated cancers and prognosis remains grim, making OGA one of the CRUK priorities.

T cell death is a master regulation process to maintain stable T cell numbers during and after infections but is largely unexplored in cancer. Our team demonstrated that response to immunotherapy is preceded by increased T cell death and preliminary results from our lab also found that the death rate of different T cell subsets can segregate cancer patients from healthy individuals. However, there are distinct T cell death mechanisms and the contribution of these to the death of distinctive T cell subsets in cancer and during immunotherapy is not known. Moreover, a deconvolution of different T cell death mechanisms in cfDNA liquid biopsies has never been performed.

This project aims to 

1) optimise a novel in vitro 3D culture microdevice to time-lapse and characterise T cell death under different experimental cell death conditions for different T cell subsets;

2) utilise this new in vitro model to identify the DNA methylome, DNA chromatin occupancy and biomarker signatures of different T cell subsets under stress and dying;

3) explore if these T cell death signatures could be deconvoluted in a cohort of tissue/liquid biopsies from patients with OGA and correlate with patient outcomes.

This project will capitalise on the diverse multidisciplinary background of our team and our extensive collaboration network. It will also have critical access to patient samples to deliver a translational study that, by dissecting one of the mechanisms of immune-evasion of OAC, has the potential to improve the precision oncology armamentarium for patients with this cancer of unmet need.

Eligibility 

You should also hold, or about to obtain, a minimum Upper Second Class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. A related master’s degree would be an advantage. 

International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. 

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How to Apply 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. On the online application form select MCRC PhD Programme. 

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.  If you have any queries regarding making an application, please contact our admissions team.  

Equality, Diversity and Inclusion  

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website. 

Applications Timeline 

Applications open: 11 October 2024 

Application deadline: 15 November 2024 

Interviews: 17th January 2025 

Start date: September 2025 

Biological Sciences (4)

Funding Notes

MCRC - CRUK Manchester Cancer Research Centre Studentship funding is for a duration of four years to commence in September 2025 and covers UK tuition fees and an annual stipend. Funding will cover UK tuition fees and stipend only.   

 

International Candidates 

We are able to offer a limited number of bursaries to high-performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges. We asses each EU and international candidate's suitability for a bursary at the application and interview stages. 


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Where will I study?

Faculty of Biology, Medicine and Health

Tackle real world challenges, make a difference, and elevate your career with postgraduate research in the Faculty of Biology, Medicine and Health at Manchester. From biochemistry to neuroscience, cancer sciences to medicine, audiology to mental health and everything in between, we offer a wide range of postgraduate research projects, programmes and funding which will allow you to immerse yourself in an area of research you’re passionate about.

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Ranked the best place to live in the UK (The Economist Global Liveability Index, 2022), Manchester boasts world-class culture, iconic sports, a thriving music and food scene, and much more. It's not just a place to research, it's a place to call home.

Experience PhD life as part of a diverse postgraduate research community of more than 1,000 postgraduate researchers at the 29th most international university in the world (Times Higher Education, 2023).

With 93% of research activity at the University rated as 'world-leading' or 'internationally excellent' (Research Excellence Framework, 2021), you'll get the chance to have an impact on global health and science challenges.

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About Faculty of Biology, Medicine and Health

At Manchester, postgraduate researchers are at the heart of our mission to tackle pressing global challenges in biological, medical and healthcare sciences - and you could be too.

By choosing Manchester for your postgraduate research, you’ll be joining a university with an exceptional research reputation, where 93% of research is world-leading or internationally excellent (REF, 2021) and where your work will have real-world impact.

You’ll research in world-class facilities alongside leading experts at the forefront of innovation, collaborating across disciplines to pioneer new treatments, advance scientific knowledge, and improve healthcare globally.

Supported by our dedicated Doctoral Academy and strong industry links, you'll experience PhD life in a vibrant, welcoming and diverse postgraduate research community.

And you’ll leave with the specialist knowledge, research experience and transferable skills that will shape your future in academia, research or industry.





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