Website The University of Manchester
Closing date: 27th November
The University of Manchester seeks a PhD student to use live imaging of the mouse brain to find out how NLRP3-positive immune cells shape the clearance of small blood clots linked to stroke, cognitive decline and dementia, on a fully funded four-year MRC NW-DMS PhD with Prof Stuart Allan, Dr Katie Murray, Dr Jack Green and Prof David Brough.
About the Project
Small blood clots accumulate in the brain throughout life and contribute to stroke, cognitive decline and dementia. Blood vessels have the capacity to remove these clots through a novel clearance mechanism called thromboangioplasticity (TAP), a vascular remodelling process whereby endothelial and smooth muscle cells reorganise around a clot, remove it from the vessel and restore cerebral blood flow (CBF). What remains unclear is how TAP is regulated, what happens to the clot after it leaves the vessel, and how immune cells contribute to this process.
Our preliminary data show NLRP3-expressing neutrophils and monocytes accumulate around blood clots. NLRP3 is an innate immune sensor that coordinates inflammatory responses to tissue damage. We hypothesise that NLRP3-positive cells have a finely balanced role: activation may support clot formation and degradation, whereas excessive inflammation may delay vessel clearance and damage surrounding brain tissue. This project will define the recruitment, identity and activation state of these NLRP3-positive cells, determine how selected myeloid populations influence TAP, and establish whether NLRP3 is a therapeutic target in clot-associated diseases.
The student will use live imaging with transgenic mouse models to follow these immune cells as vascular repair unfolds in real time. NLRP3-mScarlet reporter and knockout mice, alongside pharmacological manipulation, will be combined with flow cytometry, behaviour and molecular measures of inflammasome activation.
The project provides interdisciplinary training in cerebrovascular biology, advanced in vivo imaging and innate immunity. It will reveal whether inflammasome signalling is required for effective clot resolution or represents a therapeutic target which could have long-lasting impacts in stroke, dementia and thrombotic diseases.
https://www.braininflamelab.org/
References:
¹ Lam et al (2010) Nature 465:478–82
² Grutzendler et al (2014) Sci Transl Med 6:226ra31
³ Hoyle et al (2026) bioRxiv 2026.08.06.743215
Entry Requirements
Competition for studentships is expected to be very high.
We expect applicants to hold, or be about to obtain, a First or Upper Second-Class UK honours degree (or international equivalent) in a relevant discipline.
Due to the competitive nature of the programme, many successful applicants may also have:
- A master’s qualification.
- Relevant research experience.
- Experience demonstrating suitability for doctoral research.
Applicants who are offered a place will also need to meet the University’s English language requirements before commencing their studies. Further information can be found on the University’s English Language Requirements page.
Application Guidance
Candidates must contact the primary supervisor before applying to discuss their interest in the project and assess their suitability.
Apply directly via this link: https://tinyurl.com/h7e36xpy or on the online application portal, select MRC NW-DMS PhD Programme as the programme of study.
You can apply for up to two projects within this scheme. If you wish to apply for two projects, you must submit a separate application for each, including a supporting statement tailored to the specific project.
Please ensure that your application includes all required supporting documents:
- Curriculum Vitae (CV)
- Supporting Statement
- Academic Certificates and Transcripts
Applicants are required to provide two references as part of their application. However, these do not need to be received by the application deadline and can be submitted shortly afterwards. We ask that references are provided as soon as possible to avoid delays in the application process.
Incomplete or late applications will not be considered.
Further details are available on our website: https://www.bmh.manchester.ac.uk/study/research/funding-fees/funded-programmes/mrc-nwdp/
Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study
Funding Notes
These studentships are open to UK and international applicants and provide full funding for 4 years, covering the full tuition fees applicable to the successful applicant’s fee status (including international tuition fees for overseas applicants) and a stipend at the UKRI rate.
To apply for this job please visit www.findaphd.com.
