Innate immune recognition of danger signals is an important mechanism that protect us against infection and injury. ATP is an important danger signal released from infected or damaged cells and its extracellular presence alerts macrophages of impending danger. Extracellular ATP (eATP) binds to the P2X7 receptor, expressed on macrophages, triggering a potent pro-inflammatory immune response required to repair damage and restore health. Little is known about how P2X7R relays information from ATP binding, yet there is increasing evidence that posttranslational modifications might be key in this process. Dissecting the mechanisms inducing and controlling homeostatic inflammation triggered by ATP, and other danger siganls, will be conducive to a better understanding of the inflammatory process and a future understanding of how abnormal inflammatory responses might negatively influence health. This is especially relevant during aging as accumulation of different danger signals has been suggested to contribute to low-chronic inflammation (inflammaging) characteristic of the elderly and that in may pose them at risk of developing age-related diseases such as cancer or Alzheimer’s.
This project will address the fundamental unanswered question, how do cells respond to extracellular ATP to mediate inflammatory responses? and will investigate the molecular mechanisms underlying the response of macrophages to extracellular ATP mediated by P2X7R during inflammation. This project will provide, for the first time, a comprehensive overview of the signalling triggered by the danger signal eATP in macrophages that might be shared by a wider range of danger signals.
We are looking for enthusiastic and motivated candidates with a strong interest in cell biology and the use of molecular approaches to study a biologically fundamental question. This project includes training in a wide array of interdisciplinary techniques ranging from mass spectrometry, microscopy to antibody-based techniques such as immunofluorescence, western blotting and flow cytometry as well as gene editing by CRSPR/Cas9. The candidate will use a combination of macrophage cell lines and primary monocytes/macrophages for this project. The candidate will benefit from a stimulating environment and the cutting-edge facilities at the faculty of Biology Medicine and Health and the world-leading Lydia Becker Institute of Immunology and Inflammation. As a PhD student you will be encouraged to present your research at internal meetings as well as attending international conferences. Please email us if you are interested and would like to know more about the project.
https://www.research.manchester.ac.uk/portal/gloria.lopez-castejon.html
https://www.chiarafrancavilla.eu/
https://www.research.manchester.ac.uk/portal/philip.woodman.html
http://www.bioinf.manchester.ac.uk/schwartz/
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
How To Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
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/
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