The successful PhD candidate will discover new cell death mechanisms to kill cancer cells.
Background and Rational:
Death is not an endpoint, but the beginning of a novel communication axis between dying cells and cells of the immune system. The way in which a cell dies dramatically alters the danger signals that get released. While apoptosis tilts towards an immunologic silent outcome, non-apoptotic forms of cell death, such as caspase-independent necroptosis, can be highly immunogenic and trigger a potent anti-tumour response.
The successful PhD candidate will investigate how non-apoptotic cell death (necroptosis and pyroptosis) mechanisms can be used to open a new line of communication with immune cells. Specifically, they will study how we can rewire cell death signalling pathways into apoptosis-independent forms of cell death such as Necroptosis and Pyroptosis. They will test whether killing cancer cells by non-apoptotic forms of cell death more potently drives an immune response against tumours, hence enhancing the effectiveness of therapies.
Importantly, they will investigate cancer cell autonomous as well as non-autonomous effects, such as those mediated by cancer associated fibroblasts (CAFs) and macrophages.
Specifically, they will (i) identify strategies to enhance the ‘cell death priming’ status of cancers, (ii) gain an understanding how to rewire therapy-induced apoptosis into Necroptosis and Pyroptosis; (iii) investigate how therapy drives cGAS/STING and ZBP1 activation; (iv) characterise how we can boost the immunogenic signalling outputs of cGAS/STING and ZBP1; (v) evaluate the immunogenicity of novel treatment protocols using state-of-the-art in vivo mouse tumour models of cancer, and (vi) corroborate our findings using live tissue explants from patients.
The discovery of the molecular mechanism that can tip the balance of immunologically silent cell death (apoptosis) in favour of immunogenic cell death will be of enormous interest as new therapeutic strategies are much needed to re-activate a patient’s immune system against cancer.
What you will learn:
The student will gain valuable expertise in interdisciplinary research, building on their existing knowledge of biologal sciences. They will be supported by a supervisory team combining expertise in cell death and immunity. Working within the Cell Death and Immunity team (Prof. Pascal Meier), they will develop skills in cell death signalling, innate and adaptive immunity as well as the use of state-of-the art in vivo cancer models. Moreover, they will be trained in using patient-derived organoids and patient-derived tissue explants to study the communication between dying cells and cells of the tissue micro-environment. They will benefit also from the exposure to the immuno-oncology expertise of Prof. Alan Melcher and Prof. Kevin Harrington. Moreover, they will be supported by our in-house training programmes, along with seminars from world-leaders. Students will be supported to communicate their research widely, including writing up results for publication in peer-reviewed journals. As a result of their training, past students in our groups have readily found employment as scientists in academia or the pharmaceutical industry.
- Cell Death
- Improving Treatment
- Overcoming resistance
Candidates must have a First class or Upper Second class BSc Honours/MSc in a relevant scientific subject, including some experience in molecular biology or cell biology.
How to apply
To view the full project proposal and details on how to apply using our online recruitment portal, please go to icr.ac.uk/phds. Please ensure that you read and follow the application instructions very carefully.
Please note we only accept applications via the online application system apply.icr.ac.uk.
Applications close at 11:55pm UK time on 14 November 2021.