It would be to start in Sept 2021
About the Project
Concussion, or mild traumatic brain injury, affects millions world-wide each year due to motor accidents, falls, assaults, domestic violence, contact sports and war. It is now appreciated that a history of concussion increases the risk of developing long-term emotional and neurocognitive disorders. These include anxiety and depression, as well as neurodegenerative conditions such as Alzheimer’s. Critically, we do not know the mechanisms behind long-term negative effects of concussion on brain health.
The following project will investigate the role of infiltrating immune cells within key structures at the blood-brain interface, that we hypothesise to drive neuroinflammation and concussive symptoms after head injury.
The interfaces between the periphery and the brain are now under intense scrutiny as hubs of inflammation and potential drivers of brain injury, mood disorders and neurodegenerative disease. Two of the key blood-brain interfaces are the meninges and the choroid plexus. The meninges are a set of protective membranes that surround the brain and the choroid plexus is a structure that produces cerebrospinal fluid and is essential for a variety of brain function. Recent data has shown that the meninges and choroid plexus contain immune cells that are proposed to play important functions in the brain. Surprisingly, little is known of the role of the choroid plexus or meninges and the immune cells within them in concussion.
To address this, the project will investigate the role of innate and adaptive lymphocytes in the response to concussive injury in a clinically relevant mouse model. T cells and Innate Lymphoid Cells (ILCs) are potent regulators of the immune response, and are emerging as key players in neuroinflammation while residing in the meningeal membranes and choroid plexus. Moreover, danger signals and soluble factors known to activate lymphocytes, including ILCs, are also known to regulate brain function and recovery after injury, though it remains unknown how lymphocytes contribute to concussion-related symptoms.
We predict that a concussive-symptoms are driven by lymphocyte-dependent inflammation in the meninges and choroid plexus and can be targeted to improve outcome after injury.
This interdisciplinary project is at crossroads of neuroscience and immunology, reflected by the modelling of brain injury and assessment of emotional behaviour and cognition, while investigating fundamental immune mechanisms driving behavioural deficits.
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 Primary 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 MRC Doctoral Training Partnership (DTP) website http://www.manchester.ac.uk/mrcdtpstudentships
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 bursaries 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
Greenhalgh AD, David S, Bennett FC (2020)
Immune cell regulation of glia during CNS injury and disease.
Nature Reviews Neuroscience.
Greenhalgh AD, Healy LM, Zarruk JG, Salmon CK, Russo MV, Antel JP, McGavern DB, McColl BW, David S (2018).
Peripherally-derived macrophages modulate microglia function to reduce inflammation after CNS injury.
Sonnenberg GF, Hepworth MR (2019) Functional interactions between innate lymphoid cells and adaptive immunity.
Nature Reviews Immunology.
Melo-Gonzalez F, Kammoun H, Evren E, Papadopoulou M, Bradford B, Mabbott N, Tanes C, Fardus-Reid F, Swann JR, Bittinger K, Vallance B, Withers DR, Willinger T, Hepworth MR (2019)
Antigen presenting ILC3 regulate T cell-dependent IgA responses to colonic bacteria.
J Exp Med