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(MRC DTP) Characterisation of longitudinal peripheral immune cellular changes in post-stroke cognitive decline

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  • Full or part time
    Prof C Smith
    Dr J Grainger
    Prof S Allan
  • 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

Stroke is a major cause of death and disability worldwide. In stroke survivors one of the most distressing complications is post-stroke cognitive decline (PSCD), which occurs in up to a third of individuals within five years and impacts significantly on quality of life.

Dysregulated inflammatory and immune pathways are strongly implicated in the pathophysiology of cerebrovascular disease and have also been linked to dementia and cognitive impairment. Innate immune cells, such as microglia and monocytes, play a key role in the response to brain injury and are thought to modulate subsequent pathways involved in recovery and repair. We have recently undertaken detailed immunophenotyping of the peripheral blood myeloid compartment in acute stroke patients, and identified specific changes in dendritic cell and monocyte subsets. Our collaborators have demonstrated that specific changes in peripheral innate cells in the acute phase of stroke correlate with subsequent cognitive impairment. Our overarching hypothesis is that innate immune alterations in the acute phase after stroke shape chronic maladaptive neuroimmune responses that compromise long-term structural and functional brain integrity, and contribute to PSCD.

The main aim of this project is to Investigate the association between immune status, with a focus on myeloid sub-sets, and cognitive function after stroke in patients. The project will align with a prospective cohort study of patients with acute ischemic stroke, with longitudinal follow-up, serial blood sampling, blood bio-banking, and clinical assessments. Serial blood samples will be drawn for evaluation of immunophenotype and function of myeloid subsets using state of the art multicolour flow cytometry, RNA sequencing and immunoassay of related plasma inflammatory markers. Computational immunology algorithms will be applied to the flow cytometric analyses and single-cell RNA sequencing. Relationships with baseline clinical factors and both cognitive and functional outcomes will be explored. Comprehensive training will be provided in translational neuroscience, immunology and bioinformatics with opportunities to visit our collaborating groups to present data and learn emerging technologies and techniques. This project will provide novel insights into how the immune system is altered over time after stroke and how this relates to cognitive trajectory and possible therapeutic or preventative targets.

https://www.research.manchester.ac.uk/portal/craig.smith-2.html
https://www.research.manchester.ac.uk/portal/stuart.allan.html
https://www.research.manchester.ac.uk/portal/john.grainger-2.html

Entry Requirements:
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.

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

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.



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