Immune checkpoint immunotherapy triggers adaptive immune lymphocyte activation that can lead to effective treatment for cancer. Adaptive immune lymphocyte activation can also lead to autoimmunity—the chief toxicity of this treatment. Mechanistic studies into the efficacy of this modality has been hampered by our ability to clonally track adaptive immune cells that respond to immunotherapy. The Thaventhiran group have validated a unique preclinical system that can clonally track adaptive immune lymphocytes responding to diverse triggers. They are currently using this system with CITE-seq and single-cell RNA sequencing to study the clonal response to melanoma.
This project will use this system to characterise the full spectrum of clonal expansion and differentiation in response to immune checkpoint blockade, seeking to identify the key regulators that dictate the difference between efficacy and toxicity. The student will then demonstrate that the regulators they identify in mice are relevant in humans by studying samples from patients.
This project represents an ideal opportunity to learn a wide range of state-of-the-art techniques including cellular and molecular biology, genomics, proteomics, and bioinformatics to better understand the mechanisms of cancer immunotherapy. Development of successful models would lead to collaborations with industry.
The research will be conducted within the MRC Toxicology Unit which is a core-funded institute within the School of Biological Sciences, University of Cambridge,. This leading international research unit provides state of the art research facilities, with excellent opportunities for collaborative interaction within a vibrant community at the University of Cambridge.
Students are encouraged to attend a variety of training modules and courses, available in Cambridge within the University, EBI-Bioinformatics Institute, and Sanger Centre. In addition to the Toxicology Unit’s weekly external and internal seminar programs, students will be expected to attend the Cambridge Immunology Network seminar series and are included in the postdoc/student forums which take place each month. Together this package offers excellent opportunities for collaboration and career development.
It is recommended that you contact the supervisor prior to making your formal application: [email protected]
This studentship is for four years commencing October 2020 with an annual stipend of £15,009 (tax free).
Applications will need to be made through the University Application Portal and will entail an application fee of £65. Please enter the project title in the ‘Proposed title of Research’ textbox.
Your online application needs to include:
• A CV, including full details of all University course grades to date.
• Contact details for two academic or professional referees.
• A personal statement outlining your interest in a specific project area, what you hope to achieve from a PhD, and your research experience to date.