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(BBSRC DTP) Understanding how macrophages respond to damage-derived inflammatory signals


Faculty of Biology, Medicine and Health

About the Project

Innate immune recognition of danger signals is an important mechanism that protect us against infection and injury. ATP is 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 kinase signalling plays an important downstream role, suggesting that posttranslational modifications might be key in this process. Dissecting the mechanisms inducing and controlling homeostatic inflammation triggered by ATP will be conducive to a better understanding of the inflammatory process and a future understanding of how abnormal inflammatory responses might negative influence health. This is especially relevant during aging as ATP accumulation 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.

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


Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

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 http://www.manchester.ac.uk/bbsrcdtpstudentships

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

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 View Website

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