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Molecular modelling and analysis of plasma cell cancers


   Faculty of Medicine and Health

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  Dr R Tooze, Dr G Doody, Dr R Owen  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Plasma cell neoplasms, including multiple myeloma, are cancers of the immune system that remain largely incurable despite major advances in therapy. Diverse oncogenic events contribute to neoplastic transformation of plasma cells, but how these cooperate to impact on normal plasma cell differentiation is a matter of deduction rather than direct experimental data. This is because there have been no robust in vitro models of plasma cell differentiation and models in transgenic mice have been limited by the ability to target expression to the correct differentiation stage. We have developed an in vitro culture system that allows mature human plasma cells to be consistently generated and maintained in vitro. We are thus uniquely placed to begin modelling the impact of oncogenic events on human plasma cell differentiation. This will be the primary objective of this PhD. 

Objectives

This 3-year PhD project funded by the Ella Dickinson Charitable Foundation 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. 

The PhD student 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. The PhD student 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 a student 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.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD 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

Applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

  • Select PhD in Medicine as your programme of study
  • Give the full project title and name the supervisors listed in this advert
  • For source of funding please state you are applying for an Ella Dickinson Charitable Foundation Scholarship 

As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Within the School of Medicine we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability.

For further details about this project and how to apply please contact the Faculty Graduate School [Email Address Removed]


Funding Notes

A PhD studentship funded by the Ella Dickinson Charitable Foundation is available for UK citizens only. The studentship will attract an annual tax-free stipend of £16,062 for up to 3 years, subject to satisfactory progress and will cover the UK tuition fees.

References

TLR-mediated activation of Waldenström macroglobulinemia B cells reveals an uncoupling from plasma cell differentiation. Shrimpton J, Care MA, Carmichael J, Walker K, Evans P, Evans C, de Tute R, Owen R, Tooze RM, Doody GM. Blood Adv. 2020 Jun 23;4(12):2821-2836. doi: 10.1182/bloodadvances.2019001279. 
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. 
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. 
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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