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Molecular modelling and analysis of plasma cell cancers


Project Description

Plasma cell neoplasms, including multiple myeloma, are cancers of the immune system that remain largely incurable despite major advances in therapy. These diseases have a slow evolution and can often be detected at an early stage, but our understanding of early disease mechanisms and the opportunities for intervention are limited. One factor in this is the lack of suitable systems that allow us to model the early stages of the disease process, particularly for human cells. Using enhanced cell culture models developed in our laboratory we are now for the first time in a position to ask important questions about the initial stages of plasma cell transformation. This will be the primary objective of this PhD.

Objectives
This 3-year PhD project will utilise our unique model system of in vitro human plasma cell differentiation to analyse how oncogenes impact on the biology of these cells. The project will explore commonly deregulated oncogenes involved in myeloma origins and utilise different niche conditions that allow plasma cell survival. The PhD project will integrate a range of approaches including molecular analysis (gene expression, epigenetic profiling and single cell analysis) with flow cytometry and cellular functional studies. 

You will be principally based in the Division of Haematology & Immunology of the University of Leeds but will link to the Haematological Malignancy Diagnostic Service of Leeds NHS Trust and to the analysis of primary PC neoplasia samples. You will be able to access state-of-the-art facilities in vibrant laboratory settings, providing unique access to clinical pathology and leading research in plasma cell biology. 

Novelty
Cellular models of human disease play an increasingly important part in exploring disease mechanism and potential pathways for therapeutic intervention. This PhD offers a unique opportunity to work in this context in a human immune system cancer. Furthermore, the close working relationship between clinical and mechanistic research teams provides the basis for developing innovative and complimentary approaches to study an important and timely question.

Requirements
This is a wet-laboratory PhD suitable for an individual with drive and enthusiasm for understanding cancer biology and particularly suited to those with knowledge and interest in immunology and haematology. It would be particularly suited to those with an interest in applied patient focused research.

Eligibility
You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. This project would suit someone with a strong background in immunology, haematology, cancer biology or a closely related area, and additional experience of conducting research in a health-related discipline, for example through a masters degree, is highly desirable.

The minimum requirements for candidates whose first language is not English are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply
To apply for this project applicants should complete a Faculty Scholarship Application form using the link below https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form) and send this alongside a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School at

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to  by no later than Tuesday 10 March 2020.

If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email fmhgrad to inform us you would like to be considered for this project.

Funding Notes

A PhD scholarship is available for UK and EU citizens who are able to commence study in September/October 2020. The scholarship will attract an annual tax-free stipend of £14,825 for up to 3 years, subject to satisfactory progress and will cover the UK/EU tuition fees. This scholarship is funded by the Ella Dickinson Charitable Foundation Scholarship Programme.

References

Growth Factor-like Gene Regulation Is Separable from Survival and Maturation in Antibody-Secreting Cells. Stephenson S, Care MA, Fan I, Zougman A, Westhead DR, Doody GM, Tooze RM. J Immunol. 2019 Feb 15;202(4):1287-1300. doi: 10.4049/jimmunol.1801407. Epub 2019 Jan 14. PMID:30642980

A replicative self-renewal model for long-lived plasma cells: questioning irreversible cell cycle exit. Tooze RM. Front Immunol. 2013 Dec 18;4:460. doi: 10.3389/fimmu.2013.00460. Review.  PMID:24385976

In vitro generation of long-lived human plasma cells. Cocco M, Stephenson S, Care MA, Newton D, Barnes NA, Davison A, Rawstron A, Westhead DR, Doody GM, Tooze RM.
J Immunol. 2012 Dec 15;189(12):5773-85. doi: 10.4049/jimmunol.1103720. 

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