Developing next generation bioimaging/biophotonics tools to dissect the immunological synapse in single cells, one molecule at a time

This project aims to develop/apply new bioimaging/biophotonics tools to gain insight into complex biological processes across multiple length/timescales, from single molecules through to subcellular structures, cells and cellular populations. The student will need to be eager to embrace interdisciplinary science from biophysics through to cell/molecular biology, and will learn from world-class teams in these areas. The student will work in the Department of Biology, University of York, in the team of Prof Mark Leake (http://www.single-molecule-biophysics.org/), co-supervised by Dr Nathalie Signoret (https://www.york.ac.uk/cii/staff/academic/signoret/). This project is supported by the National Physical Laboratory (NPL), the UK National Measurement Institute, jointly supervised by Mike Shaw (http://www.npl.co.uk/people/mike-shaw) from NPL's Biometrology group; the student will spend 12 months at NPL's main site in Teddington, SW London. The project focuses on understanding how the Immunological Synapse (IS) forms and is regulated. The IS defines contact processes of immune cells communication, which in the case of T cell-macrophage interactions is crucial for a host response to infection. However, key mechanistic details concerning IS formation/regulation are unknown due to focusing on too narrowly defined length/timescale regimes. You will develop cross lengthscale imaging/photonics tools to enable insight into the dynamic complexities of IS formation/regulation in cells, involving rapid single-molecule detection and quantification in vivo combined with nanoscale spatial precision (see Miller et al 2018 PMID 29872430; Wollman et al 2017 PMID:28841133; Kasprowicz et al PMID:29789661; Shaw et al PMID 25839410).

The project aims to add new understanding in how chemokine stimulation is used for regulation of IS formation, focusing on chemokine receptor CCR5, with initial investigations on model cell-lines to address basal CCR5-ligand behaviour before moving to more challenging primary macrophages and IS formation with T cells, probing dynamics of chemokine receptor-ligand interactions, chemokine binding to cell-surface proteoglycan, and local membrane lipids and proteins interactions during IS formation.