Website The University of Sheffield
Details
The engulfment of pathogens by phagocytic immune cells is key to protect the body from infection. This shares much of the same cellular machinery as the engulfment of extracellular fluid by macropinocytosis, which also helps immune cells survey for antigens, as well as enabling cancer cells to grow by feeding on extracellular proteins.
However, in the process of engulfment, cells also take up part of their own surface. This means they have to retrieve their own proteins from the vesicles formed before they get destroyed along with the captured material. Our previous work has shown that if cells cannot do this, they can no longer function properly.
The aim of this PhD project is to apply cutting-edge microscopy, genetics and biochemistry to understand the fundamental mechanisms of how cells process phagosomes and macropinosomes to retrieve membrane proteins and therefore sustain both immune and cancer cell function.
Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying
Funding Notes
This project is available for self-funded applicants only
References
Recent papers from our group:
Buckley CM, Gopaldass N, Bosmani C, Johnston SA, Soldati T, Insall RH, King JS. WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors. Proceedings of the National Academy of Sciences, USA. 2016 Oct 4;113(40):E5906-E5915 https://www.pnas.org/doi/abs/10.1073/pnas.1524532113
CM Buckley, R Potts, A Gueho, JH Vines, CJ Munn, BA Phillips, B Gilsbach, A Nikolaev, T Soldati, AJ Parnell, A Kortholt and JS King†. Coordinated Ras and Rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria. Current Biology, 2020. 30, 2912–2926. https://www.cell.com/current-biology/fulltext/S0960-9822(20)30736-3
JH Vines, Maib, CM Buckley, A Gueho, Z Zhu, T Soldati, DH Murray, JS King†. A PI (3, 5) P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes. Journal of Cell Biology, 2023. 222 (9): e202209077. https://rupress.org/jcb/article/222/9/e202209077/214199
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