Deadline: The closing date for applications is 15 November 2020, with interviews expected to take place in December/January.
The Cancer Research UK Cambridge Institute (CRUK CI) is a joint venture between the Charity, Cancer Research UK, and the University of Cambridge. The Institute has excellent state-of-the-art facilities and research ranges from basic cancer biology and computational biology through to translational research and clinical application. Graduate students play a pivotal role in the continuing success of our research programmes and gaining a studentship in the Institute is an excellent opportunity to start a research career in an environment committed to training outstanding cancer research scientists of the future. For further information, go to: https://www.cruk.cam.ac.uk/jobs-and-studentships/postgraduate-study
Dr Raza Ali wishes to appoint a student to work on the project entitled: High dimensional tissue imaging to track genomic selection by immune predation in situ in breast cancer.
For further information about the research group, including their most recent publications, please visit their website: https://www.cruk.cam.ac.uk/research-groups/Ali-group
Project description: The repertoire and spatial localisation of tumour infiltrating leukocytes impact breast cancer outcomes (reference 1). Early trials also indicate that some patients with triple-negative breast cancer stand to benefit from immunotherapies (references 2,3). But which patients benefit and what mechanisms underpin resistance are not known. Tumour evolution is driven by ongoing somatic mutation. There is evidence that predation by the immune response selects for fitter genomic clones able to effect immune escape (e.g. by gain of CD274 [PD-L1] (references 4,5)). But when immune selection takes place during the trajectory of disease progression is not known. Similarly, it is not clear whether this process shows spatial variation, which would lead to regional purifying selection with implications for disease dissemination and immunotherapy response. We use high-dimensional imaging (imaging mass cytometry [IMC]) to study the dynamic ecosystems of breast tumours (reference 5). This project will aim to develop these techniques to answer the following: (1) Can genomic clones be reliably identified in situ? (2) Is spatial clonal enrichment explained by the local tumour-immune microenvironment? (3) If so, when during the process of disease progression does immune selection occur? To address these questions, the student will develop highly multiplexed composite RNA/protein IMC assays (reference 6) for application to patient breast tumour tissues, and use sophisticated image analysis techniques and computational biology to arrive at quantitative conclusions.
References:
- Ali, H. R., Chlon, L., Pharoah, P. D., Markowetz, F. & Caldas, C. Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study. PLoS Med 13, e1002194, doi:10.1371/journal.pmed.1002194 (2016).
- Nanda, R. et al. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol, doi:10.1200/jco.2015.64.8931 (2016).
- Mittendorf, E. A. et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet, doi:10.1016/s0140-6736(20)31953-x (2020).
- Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G. & Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160, 48-61, doi:10.1016/j.cell.2014.12.033 (2015).
- Ali, H. R. et al. Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer. Nature Cancer 1, 163-175, doi:10.1038/s43018-020-0026-6 (2020).
- Schulz, D. et al. Simultaneous Multiplexed Imaging of mRNA and Proteins with Subcellular Resolution in Breast Cancer Tissue Samples by Mass Cytometry. Cell systems, doi:10.1016/j.cels.2017.12.001 (2017).
Qualifications/skills: This project is well suited to applicants with a background in systems biology, and those with an interest in cancer research at the clinical interface. Strong candidates with backgrounds in immunology or molecular biology lacking training in computational methods, but with a keen interest to learn, are also encouraged to apply. This role will provide extensive training in cancer pathology, high dimensional imaging and computational biology.
Funding: This project is funded by a Cancer Research UK studentship that includes full funding for University and College fees and a stipend of £19,000 per annum.
Eligibility: No nationality restrictions apply to Cancer Research UK funded studentships. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree (or equivalent) in a relevant subject from any recognised university worldwide.
How to apply: All applications need to be made using the University Applicant Portal. Please visit: https://www.graduate.study.cam.ac.uk/courses/directory/cvcrpdmsc for further information about the course and to access the applicant portal.
To complete your on-line application, you need to provide the following:
Reference Request: The names and contact details of two academic referees who have agreed to act on your behalf.
Research: If you wish to be considered for more than one studentship, please enter the names of all of the supervisors you wish to consider your application in the ‘Research summary’ text box. If you only wish your application to be considered by a single supervisor, then please enter their name in the ‘Research Supervisor’ text box. Please describe your past ‘Research experience’ in the appropriate text box.
Course Specific Questions: Your statement of interest (limit of 2,500 characters) should explain why you wish to be considered for the studentship and which qualities and experience you will bring to the role. Please also state how you learned of the studentship.
Supporting Documents: Please upload your CV (PDF file), which should include a list of the examinations taken at undergraduate level and if possible, your examination results
Deadline: The closing date for applications is 15 November 2020, with interviews expected to take place in December/January.
Please quote reference SW24235 on your application and in any correspondence about this vacancy.
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