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About the Project
As we age, the systems of our bodies become less able to function; rendering people increasingly infirm. Ageing affects our immune system, impeding our ability to both fight infection and maintain tolerance. At barrier sites, such as the gut and oral barrier, this is a particular problem. The immune system at these barriers is delicately balanced; protecting against pathogens yet also distinguishing these invaders from the commensal-bacterial communities inhabiting these sites. To achieve this, immune responses at barrier sites are carefully tuned to their commensal partners and a successful host-microbe dialogue is established. Maintaining this balance becomes difficult as we age.
The influence of age on oral bacterial communities is minimally explored and how these evolving communities tune immune function is unknown. This is an oversight, as advancing age is accompanied by failure of oral barrier immune-homeostasis, resulting in increased incidence and severity of oral inflammation, particularly periodontitis. Critically, periodontitis is a risk factor for multiple disorders promoting unhealthy ageing, including cardiovascular disease and diabetes. Therefore, elucidating factors driving loss of oral barrier immune-homeostasis and development of inflammation is urgently required.
We hypothesize that an altered host-microbe dialogue promotes dysregulation of oral barrier immune responses with age. This project will outline how oral bacterial communities are remodelled during ageing and, importantly, the influence of this altered bacterial community on oral barrier immune functions. Collectively this work will further our understanding of how oral barrier inflammation arises with age, promoting development of therapeutics to reinforce oral barrier immune-homeostasis across a life-course.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
How 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 Genetics
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.
Equality, Diversity and Inclusion
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 https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
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
Informal enquiries may be made directly to the primary supervisor.
References
2) Eskan M.A., et al., The leukocyte integrin antagonist Del-1 inhibits IL-17 mediated inflammatory bone loss. Nat Imm. 2012. 13, 465-473.
3) Hajishengallis G., et al., Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host and Microbe. 2011. 10(5). 497-506.
4) Claesson, M.J., et al., Gut microbiota composition correlates with diet and health in the elderly. Nature, 2012. 488(7410): p. 178-84.
5) Zanvit P., et al., Antibiotics in neonatal life increases murine susceptibility to experimental psoriasis. Nat Commun. 2015. 6(8424).
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