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Characterising the faecal virome in Crohn’s disease patients with known NOD2 variants compared to matched controls without gastrointestinal disease (ref: SF18/APP/Bridge)

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The human virome includes viruses that infect host cells and viruses that infect bacteria, and impacts on health and disease independently of classical viral disease. Changes in intestinal viruses have been found in patients with inflammatory bowel disease (IBD) such as Crohn’s disease (CD), indicating that changes in the virome might be a potential trigger of CD or it may influence disease progression.

Tremendous progress has been made in identifying the genes that predispose to CD e.g. NOD2. However, little is known about the interactions between NOD2 variants with the intestinal virus community. Further detailed investigation of these interactions are necessary and will reveal important information regarding what goes wrong when Crohn’s disease develops.

This PhD projects seeks to test the hypothesis that changes in the enteric virome drives the immunological switch from tolerance to inappropriate inflammation within the gastrointestinal tract of patients with CD compared to appropriately matched controls. This research will use next generation sequencing and bioinformatics to compare the virome in patients with CD to carefully matched controls without gastrointestinal disease. There is further opportunity to investigate and model the interactions between bacterial, fungal and viral communities.

The student will gain significant in-house expertise and training in nucleic acid extraction methods, next generation sequencing and bioinformatics. Cross-disciplinary training will be provided in molecular biology, microbial ecology, infection and immunity.

The findings of this translational research project will further define the role of microbial dysbiosis in CD and what contribution the enteric virome plays in the pathophysiology of the disease. It is hoped that the results of this study will guide identification and development of novel therapies for CD.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. RDF18/…) will not be considered.
Deadline for applications: 1st July for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: March or October 2019

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers

Funding Notes

This studentship is only open to self-funding candidates. Self-funding candidates are expected to pay University fees and to provide their own living costs. University fee bands are shown at
View Website
Projects in Applied Sciences are typically costed at Band 3 or Band 4.

References

Holt, G. S., Lodge, J. K., McCarthy, A. J., Graham, A. K., Young, G., Bridge, S. H., Brown, A. K., Veses-Garcia, M., Lanyon, C. V., Sails, A., Allison, H. E. and Smith, D. L. (2017) 'Shigatoxin encoding Bacteriophage ɸ24B modulates bacterial metabolism to raise antimicrobial tolerance', Sci Rep, 7, pp. 40424.
Kennedy, N. A., Lamb, C. A., Berry, S. H., Walker, A. W., Mansfield, J., Parkes, M., Simpkins, R., Tremelling, M., Nutland, S., Consortium, U. I. G., Parkhill, J., Probert, C., Hold, G. L. and Lees, C. W. (2018) 'The Impact of NOD2 Variants on Fecal Microbiota in Crohn's Disease and Controls Without Gastrointestinal Disease', Inflamm Bowel Dis, 24(3), pp. 583-592.
Norman, J. M., Handley, S. A., Baldridge, M. T., Droit, L., Liu, C. Y., Keller, B. C., Kambal, A., Monaco, C. L., Zhao, G., Fleshner, P., Stappenbeck, T. S., McGovern, D. P., Keshavarzian, A., Mutlu, E. A., Sauk, J., Gevers, D., Xavier, R. J., Wang, D., Parkes, M. and Virgin, H. W. (2015) 'Disease-specific alterations in the enteric virome in inflammatory bowel disease', Cell, 160(3), pp. 447-60.
Tariq, M. A., Everest, F. L., Cowley, L. A., De Soyza, A., Holt, G. S., Bridge, S. H., Perry, A., Perry, J. D., Bourke, S. J., Cummings, S. P., Lanyon, C. V., Barr, J. J. and Smith, D. L. (2015) 'A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients', Front Microbiol, 6, pp. 97.

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