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Postgraduate Admissions

 

Pancreatic cancer is a lethal disease with a dismal prognosis, with an overall 5-year survival rate of less than 9%. Pancreatic Cancer UK has launched a Future Leaders Academy to improve our understanding of tumour-stromal and tumour-immune interactions in the hope of identifying therapeutic targets in pancreatic ductal adenocarcinoma (PDAC).

The most common type of pancreatic cancer (PDAC) is characterized by its striking fibroinflammatory stroma, which constitutes some 90% of tumour bulk. The stroma is generally thought to promote tumour growth by inhibiting the tumour immune system, providing growth factors and contributing to PDAC therapeutic refractoriness by impeding vascular perfusion and oxygenation, although recent evidence suggests that elements of the stroma have tumour-restraining properties.

Strategies targeting the stroma in PDAC have so far focused mainly on fibroblasts, specific components of the extracellular matrix such as hyaluronan, or angiogenesis. Although preclinical results were promising, in most cases this did not translate in the clinical setting. Pancreatic tumours are also resistant to immunotherapies that work in other cancers, such as PD-1/PD-L1 immune checkpoint blockade and anti-CTLA-4 antibodies. There is, therefore, a need for further research into the microenvironment of pancreatic tumours, to understand the interactions that influence pancreatic tumour development and growth, and to overcome resistance to treatment.

Dr Tim Halim wishes to appoint a student to work on the project entitled: Visualising ILC2/Treg interactions in the pancreas during pancreatic carcinogenesis. For further information about the research group, including their most recent publications, please visit their website - https://www.cruk.cam.ac.uk/research-groups/halim-group

Project details
Our aim is to understand the role of tissue-resident immune cells that we have identified in the pancreas, namely ILC2 (group 2 innate lymphoid cells). ILC2 are recently discovered immune cells belonging to the innate lymphoid lineage, that have roles in mucosal barrier immunity, wound healing responses and M2 macrophage polarisation (Schuijs M.J. et al.,2018). We have recently demonstrated that in other organs, ILC2 can regulate other lymphocytes that are known to be important in different aspects of cancer immunity (Schuijs M.J. et al. 2020, Halim T.Y. et al., 2018, Stocks J. et al. 2019). We have developed experimental models that allow us to carefully dissect the role ILC2 at different stages of PDAC progression. Ultimately, we aim to discover key immune-regulatory functions of ILC2 in the pancreas that may serve as novel targets for anti-cancer therapy.

The project will leverage existing strengths of the Halim lab in ILC2 biology, basic and tumour immunology, models of pancreatic carcinogenesis, and equipment and expertise established at the CRUK CI. The successful applicant will have the ability to rapidly acquire the technical training from senior lab members, and develop their own project, which includes: Creating more refined reagents to study ILC2 interactions in tumour and non-tumour environments, using high-parameter flow cytometry or imaging platforms to disentangle immune cell interactions, developing in vitro and in vivo assays to study ILC2 interactions.

Key references
Schuijs MJ et al. (2020) ILC2-driven innate immune checkpoint mechanism antagonizes NK cell anti-metastatic function in the lung. Nat Immunol. 21, 998¿1009. (https://doi.org/10.1038/s41590-020-0745-y)

Halim T et al. (2018) Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells. Immunity (http://doi.org/10.1016/j.immuni.2018.05.003)

Stockis J et al. (2019) Regulation of regulatory T cells in cancer. Immunology (http://doi.org/10.1111/imm.13064)

Schuijs MJ et al. (2018) Group 2 innate lymphocytes at the interface between innate and adaptive immunity. Ann NY Accad. Sci.(http://doi.org/10.1111/nyas.13604)

Qualifications/skills
The successful applicant will have a strong academic background with prior research experience, with relevant training in basic immunology, cancer biology, and molecular biology. Training in bioinformatics and/or IF microscopy is beneficial. The PhD student will work in a dynamic and collaborative environment; valued personal qualities include teamwork skills, creativity, curiosity and strong initiative. Building on promising preliminary data, and leveraging cutting-edge reagents, core-resources and established expertise, we believe that this ambitious project has the foundation to both succeed and reveal important information about the immunology of pancreatic cancer.

Funding:
This studentship is funded by the Pancreatic Cancer UK Future Leaders Academy that includes full funding for University and College fees, a stipend of £19,000 per annum over a period of 4 years, and funding for consumables.

Eligibility
No nationality restrictions apply to this studentship. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree (or equivalent) or Master's degree 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.

Please indicate that you wish to be considered for Cambridge Trust funding.

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 in CRUK CI, 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.

The closing date for applications is 22 November 2020, with interviews expected to take place in December/January.

Key Information

Cancer Research UK Cambridge Institute

Reference: SW24420

Dates and deadlines:

Published
Thursday, 15 October, 2020
Closing Date
Sunday, 22 November, 2020