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About the Project

Concussion, or mild traumatic brain injury, affects millions world-wide each year. 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 the immune system across different brain regions that may be differentially susceptible to injury. We hypothesise that region-specific neuroinflammation drives and concussive symptoms after head injury.

Microglia and the interfaces between the periphery and the brain are now under intense scrutiny as hubs of inflammation. 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. Little is known of the role of these areas and their immune cells in concussion and how they may communicate to microglia and drive neuroinflammation.

To address this, the project will investigate the role peripheral immune cells and their communication to microglia in concussive injury in a clinically relevant mouse model. We predict that a concussive-symptoms are driven by peripheral immune cells that drive microglial-mediated neuroinflammation.


Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related biological/life science, though candidates from other STEM backgrounds will be considered. Candidates with experience previous wet lab experience and especially those from underrepresented minorities are encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Immunology.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

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

References


Greenhalgh AD, David S, Bennett FC (2020)
Immune cell regulation of glia during CNS injury and disease.
Nature Reviews Neuroscience.
Mar;21(3):139-152.

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.
PLoS Biology
Oct 17;16(10):e2005264

Sonnenberg GF, Hepworth MR (2019) Functional interactions between innate lymphoid cells and adaptive immunity.
Nature Reviews Immunology.
Oct;19(10):599-613.

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
Apr 1;216(4):728-742

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