Applications are invited for a research studentship leading to the award of a PhD degree. The project will be based in Prof. Dan Davis’s laboratory, based in the South Kensington campus of Imperial College London, funded by a collaboration with the pharmaceutical company Bristol Myers Squibb, based in the USA. The post is supported by a bursary and fees (at the UK student rate only) funded by the pharmaceutical company Bristol Myers Squibb for 3.5 years. You will join an international team of several postdoctoral researchers and other PhD students, supported by a variety of funding sources, all working on a range of related projects using microscopy to study immune cell recognition of diseased cells.
This project will study fundamental aspects of molecular recognition of cancer cells by human immune cells, especially CAR T cells, using super-resolution fluorescence microscopy alongside many molecular and cell biology techniques. The overall aim is to optimize CAR T cell immune therapies for cancer treatment.
We and others have found that, in general, immune cell receptors and ligands are organised into micrometer and nanometer-scale domains at cell surfaces. We have found that the size and composition of these nanoclusters are correlated with immune cell activation and inhibition. For example, the dynamism of receptor nanoclusters can impact signalling by sequestering inhibitory receptors away from activating ones. Alternatively, synergistic signalling can be triggered when different receptor clusters coalesce. These emerging features of immune cell surface dynamics represent a paradigm shift in how immune responses can be switched on or off. There is very little understanding of how this plays out for CAR T cell recognition of cancer cells, especially comparing different types of CAR T cell.
Tackling this will provide the knowledge necessary for the rationale design of the optimal CAR T cells for therapeutic use. Thus, this project will assess the impact of various different configurations of CAR T cell in terms of how well they recognize cancer cells, their functional responses, and the dynamics of the cell-cell interactions, including analysis of the membrane organization of the relevant receptors, ligands and signaling molecules.
Understanding the molecular mechanisms by which CAR T cells interact with cancer cells will seed new ideas for what makes a CAR T cell work best. This project offers a student the opportunity to gain a rare set of skills in state-of-the-art microscopy, a wide range of molecular and cellular biology techniques, including flow cytometry, as well as an insight into cancer, inflammation and immunotherapy. In addition, the combination of basic research in a world-leading University and collaboration with a world-leading major pharmaceutical company will provide much sought-after training for any future scientific career.
The PhD program in the Department of Life Sciences will also offer opportunities for training in public speaking, writing papers and other skills. The Davis lab also plays a major role in various public outreach activities, with Prof. Davis having published three popular-level books about immunology. Imperial College London is thrilled to have been recently named University of the Year 2022 by The Times and Sunday Times Good University Guide.
Requirements and eligibility
The studentship provides 3.5 years of funding. Applicants should have a BSc honours degree (at least 2.1 or equivalent) in Biology, Biochemistry, Immunology, Biomedical Sciences or any related discipline. Applicants with a Masters degree (at Merit level or better) in addition to the BSc will be given preference. Interdisciplinarity may be given preference. Intellectual ability, enthusiasm and self-motivation are essential.
How to apply:
Please direct any questions to Prof. Daniel M. Davis ([Email Address Removed]). To apply, please email a single PDF file including: a brief cover letter describing your relevant interests and research experience, your C.V. and names and contact information of three referees. Applications will be considered as they are received, so early applications are encouraged. Closing date: March 1st 2023, but applications may close earlier than the advertised deadline if a suitable candidate is found. Start date of this PhD is flexible, according to the student’s wishes, but likely to be between April and October 2023.
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