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(MRC DTP) Understanding what causes the brain to bleed

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  • Full or part time
    Dr D Brough
    Prof S Allan
    Dr A Parry-Jones
    Dr Hiren Patel
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Acute cerebrovascular disease remains a major area of unmet clinical need and can present as a range of clinical conditions, from periventricular haemorrhage in preterm babies, through subarachnoid haemorrhage (SAH), ischaemic and haemorrhagic stroke (1). Cerebral cavernous malformations (CCMs) are common vascular malformations occurring within the brain that predispose the affected individual to an increased risk of haemorrhage. It was recently reported that the formation of CCMs in a rodent model was dependent upon TLR4-driven inflammation (2). The NLRP3 inflammasome is a multi-molecular complex that drives inflammation and is an emerging therapeutic target for many major diseases including brain haemorrhage. The NLRP3 inflammasome also requires a TLR4-dependent priming step. In this project we will test the hypothesis that CCM formation and increased haemorrhage risk is NLRP3 dependent. We have developed a unique suite of tools and reagents for interrogating NLRP3 dependent responses and this represents an outstanding opportunity to identify new therapeutic targets and strategies for a disease with a massive unmet clinical need.

https://www.bmh.manchester.ac.uk/research/domains/neuroscience-mental-health/stroke/

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

References

(1) Galea J & Brough D, The role of inflammation and interleukin-1 in cerebral ischaemia. Journal of Inflammation Research, 2013, 6:121-128

(2) Tang et al., Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature, 2017, 545:305-310


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