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The nanoscale organisation of immune cell surfaces in health and disease


   Faculty of Biology, Medicine and Health

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  Prof D Davis  Applications accepted all year round  Self-Funded PhD Students Only

Manchester United Kingdom Biophysics Cell Biology Immunology Molecular Biology

About the Project

Super-resolution microscopes, celebrated in the 2014 Nobel Prize for Chemistry, are one of the tools that allow us to study immune cells in unprecedented detail. Recently, my research team has used these microscopes to study the changing arrangements of molecules on the surface of immune cells as they survey other cells for signs of disease. My lab now aims to compare how the surface organisation of Natural Killer cells and macrophages, varies in health and disease, as well as in individuals with variations in immune system genes. We will test how the structure of cell surfaces impacts the thresholds at which immune responses are turned on and off. As well as understanding how immune cells work, we hope to uncover new ways in which medicines can nudge their activity up or down.

A PhD project is available to explore how the nanoscale organisation of cell surface proteins impacts signaling thresholds in human Natural Killer cells. A particular unknown is what mechanisms are important is how receptors are organised at the cell surface. Here, we will study how the cytoskeleton, lipid rafts, and tetraspanin scaffold proteins impact the clustering of cell surface receptors, and in turn how this impacts downstream signaling and overall immune responses. This project is highly multi-disciplinary – involving state-of-the-art and novel microscopy, quantitative image analysis as well as molecular and cell biology. This project will run in conjunction with a £1.8m WT Investigator Award to our lab to broadly investigate how the nanoscale organisation of immune cell surfaces impacts health and disease.

The project is highly multi-disciplinary – involving state-of-the-art and novel microscopy, quantitative image analysis and cell biology, and the use of clinical samples. Davis’s lab has published over 100 papers in imaging immune cell biology. Many PhD students from Davis’s lab have gone on to high-level positions afterwards, in academia or in industry, including posts in Harvard University, Oxford, Cambridge and several now hold major permanent faculty positions.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk


Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website).

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website). Informal enquiries may be made directly to the primary supervisor.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

References:
1. Davis. D.M. The Beautiful Cure, Vintage paperback (2019)
2. Lopes F, Balint S, Valvo S, Felce JH, Hessel E, Dustin ML, Davis DM, Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages, J. Cell Biol, 216, 1123-1141, (2017).
3. Davis D.M., How studying the immune system leads us to new medicines Lancet, 391, 2205-2206, (2018).
4 Bálint S., Lopes F.B., Davis D.M., A Nanoscale Reorganization of IL-15 Cytokine Receptor is Triggered by NKG2D in a Ligand Dependent Manner, Science Signaling, 11, 525, eaal3606, (2018).
5. Srpan K., Ambrose A., Karampatzakis A., Saeed M., Cartwright A.N.R., Guldevall K., Dos Santos Cruz De Matos G., Önfelt B., Davis D.M., Unzipping the Natural Killer cell immune synapse by shedding CD16, J. Cell Biol, 17, 3267-3283, (2018).