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(MRC DTP) Longitudinal interactions between the respiratory metagenome and immune fitness

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  • Full or part time
    Prof N Papadopoulos
    Dr T Gilman
  • 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

An increasing body of evidence is linking microbiome composition with human health. Chronic inflammatory diseases, such as allergy and asthma, have been associated with dysbiotic microbiomes at both the gut and the respiratory niches. Nevertheless, causality, key underlying mechanisms as well as the prognostic potential of these associations are just starting to get explored. Some of the first data in relation to the elusive viral component of the respiratory microbiome – the virome – and its dysbiotic properties, have been explored by our group in the context of the Horizon2020 project CURE. A key finding is a deficiency of prokaryotic viruses in asthma; (bacterio)phages who have the capacity of regulating the bacterial composition of the microbiome and thereby contribute to an ‘anti-inflammatory’ signalling, are reduced in number and diversity. However, phages do not appear to have direct effects on most of the human immune cells or the respiratory mucosa. It remains completely unknown if and how viral composition and signalling may interact with the host immune system and whether this has an influence on the defective immunity and exaggerated inflammation observed in asthma.
This project aims at understanding the mechanisms of interactions between the dynamic composition of microbiological communities in the respiratory tract with the immune environment they help shape and vice-versa, as well as how this may be reflected in clinical symptoms.

Specific goals include:
1. Correlating microbiological with immunological as well as clinical data obtained in the course of the longitudinal CURE project
2. Modelling potential effects of key immune components, such as interferons, on viral-bacterial interactions, and confirming the results in cellular models
3. Assessing the in-vitro effects of microbiological components on immune cell maturation and related responses.

The student will interact with the CURE team, gaining invaluable insight on medical, immunological, virological and ecological aspects of dysbiosis in a chronic inflammatory disease such as asthma, with the potential of expanding it to similar pathophysiologies. The project is interdisciplinary and intensely quantitative. The student would benefit from excellent training in bioinformatics, mathematics, immunology and biology. They will be encouraged to specify their own research directions and explore novel approaches.

https://www.research.manchester.ac.uk/portal/nikolaos.papadopoulos.html
https://scholar.google.com/citations?user=sc0m4EUAAAAJ
https://www.research.manchester.ac.uk/portal/tucker.gilman.html
https://www.research.manchester.ac.uk/portal/mark.muldoon.html
https://www.cureasthma.eu/

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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