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PhD studentship: Analysis of T cell function in smouldering myeloma

Studying T cell function and responses in the bone marrow environment of patients with smouldering myeloma.

  • Primary supervisor: Prof Kwee Yong and Prof Sergio Quezada
  • Secondary supervisors: Prof Benny Chain and Dr Javier Herrero

This is a 4-year PhD studentship funded by Cancer Research UK, which covers tuition fees at Home/EU rate and a stipend of £21,000 per year.  Due to funding body restrictions, students will need to qualify as UK/EU fee payers.

Applications to this project have closed (Monday 31 August 2020)

Project

The UCL Myeloma and Tumour Immunotherapy groups are seeking a talented and enthusiastic PhD candidate to study T cell function and responses in the bone marrow environment of patients with smouldering myeloma. Smouldering myeloma is a pre-cancerous condition that carries a 50% risk (over 5 years) of developing into the bone marrow cancer called multiple myeloma. Our laboratory seeks to understand the role of the tumour immune environment in the transformation to malignant disease. This interdisciplinary project funded by Cancer Research UK Early Detection programme aims to identify the key molecular pathways that govern T cell function in the marrow of patients with smouldering myeloma, and how these are altered during the progression to cancerous disease. The UCL myeloma laboratory uses primary bone marrow samples from patients to interrogate immune function, correlating with clinical features and outcomes. This project on smouldering myeloma is in collaboration with the DanaFarber Cancer Institute and the Broad Institute, Harvard University.

The student will work within the Yong, Quezada and Chain laboratories, with additional bioinformatics supervision provided by Dr Javier Herrero. The underlying hypothesis is that the transition from precancerous to cancerous state is driven by a combination of cell intrinsic (e.g. (epi)genomic changes) and extrinsic (especially immune microenvironmental) factors. The student will use machine learning and computational statistics to analyse and integrate data from bulk RNA sequencing, single cell sequencing, high parameter flow and mass cytometry, T-cell receptor (TCR) sequencing and spatial mapping of bone marrow cells to generate models of tumour development and progression. Specifically, the student will develop interpretable (white box) mathematical and computational models which can integrate these diverse data modalities and provide insight into the mechanistic processes which drive the transition to full malignancy.

The infrastructure to generate the data for the project is in place, in the form of core facilities for single cell sequencing (10X genomics), flow and mass cytometry, TCR sequencing with dedicated technical support, and laboratory scientists. The Early Detection programme in myeloma is supported by a dedicated technician, a post-doctoral scientist and clinical research fellow who will secure, process and analyse patient bone marrow samples to generate the requisite data. Day-to-day supervision is provided by junior post-doctoral

scientists working in the Yong, Quezada and Chain groups, and bioinformatics support is provided by the Bill Lyons Bioinformatics suite under the leadership of Dr Javier Herrero.

More detailed information about the research project is available on request from: kwee.yong@ucl.ac.uk and s.quezada@ucl.ac.uk 


Person specification

Essential 

  • Strong track record of independent learning, complex problem solving, acquiring new skills and working in a team 
  • Potential to develop expertise in new areas of the subject. 
  • Potential for innovation and initiative, and able to work independently 
  • Effective communication skills in both written and spoken English. 
  • Minimum upper second class Honours Degree in an associated discipline, or an overseas qualification of an equivalent standard. 
  • Experience in computational biology and a good understanding of NGS-based genome, epigenome or transcriptome analysis  
  • Hardworking, motivated and passionate about cancer immunology 
  • Evidence of motivation for and understanding of the proposed area of study 

Desirable 

  • Familiarity with basic T cell immunological concepts and the field of tumour immunotherapy will be desirable.  
  • Knowledge of haematological cancers  
  • Relevant experience in cancer immunology or haematology 

Students will also need to qualify as UK/EU fee payers and meet UCL general admissions criteria.

Duties and responsibilities

Research 

  • To present results regularly at lab meetings and prepare data for presentation and publication 

  • To work with other Scientists within the team as necessary. 

  • To work safely by adhering to all University policies and practices, including preparing and following laboratory risk assessments, and complying with Health and Safety policies, ethical approval processes and Human Tissue Act guidelines. 

  • To apply highly specialist scientific skills and expertise to lead in the delivery of high quality research and the preparation of high-impact research publications. 

  • To keep abreast of current developments in this research area. 

  • To report research progress to the supervisory team, the Cancer Institute, and at scientific conferences and meetings. 

  • To keep meticulous and comprehensive records of all experimental and analytical work, providing regular updates to supervisors and research teams 

Analytical and Judgement Skills 

 

  • To demonstrate a high-level of technical and analytical skill to resolve highly complex scenarios, requiring analysis, interpretation and expert judgement to find the most appropriate solutions. 
  • To identify, interpret and integrate information from a wide variety of sources, and critically evaluate the quality and assumptions of these data. 
  • To show initiative and the ability to make decisions in areas where no previous work has been undertaken. 
  • To show awareness of your own developmental needs and undertake appropriate training where appropriate. 
  • To comply with professional codes of conduct. 
Research environment

The UCL Cancer Institute is a state-of-the-art institute to consolidate cancer research at UCL and promote links with our partner teaching hospitals, in order to support excellence in basic and translational studies. The Institute draws together talented scientists who are working together to translate research discoveries into developing kinder, more effective therapies for cancer patients. It is a Cancer Research UK and Experimental Cancer Medicine Centre, and contains approximately 580 staff, including 120 PhD and MD (Res) students and 40 MSc students. Core facilities within the Institute include: Genomics Facility (gene expression microarrays); Proteomics Facility; Imaging and Cell Sorting (confocal, time-lapsed microscopy, MoFlo FACS); Pathology Suite (laser capture microdissection, tissue arrays); Experimental Imaging (with UCL Institute of Child Health); and Transgenesis. 

Application

Applications to this project are now closed (Monday 31 August 2020)

Queries: CI.Scholarships@ucl.ac.uk.