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Ultrastructural analysis of the mouse whipworm as a model for human trichuriasis

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

Project Description

Gastrointestinal dwelling nematode parasites are extremely successful parasites of both man and animals infecting over a billion people worldwide and are responsible for considerable morbidity and ill health worldwide. Of these whipworm (Trichuris trichiura) infects around 1 in 15 of the world population. Our laboratory has been at the forefront of research into whipworms using the natural mouse model Trichuris muris. Despite our detailed understanding of the host immune response to T. muris infection, our basic understanding of the biology and morphology of the parasite is extremely poor at the ultrastructural level. As parasites that have adapted to living in the intestinal epithelium, a detailed understanding of the anatomical relationship of the parasite to the host and a spatiotemporal analysis of important genes that they express will be key to moving the field forward. The project will build on the work we carried out defining the genome of Trichuris and involve scanning, transmission and 3D electron microscopy together with immunoelectron microscopy, light microscopy and gene analysis. The project will utilise state of the art equipment and infrastructure in our imaging core facilities. The student will be embedded within a well-funded group studying parasites and immunity, part of the Lydia Becker Institute of Immunology and Inflammation and the Wellcome Centre for Cell Matrix Research.

The project will involve scanning, transmission and 3D electron microscopy together with immunoelectron microscopy, light microscopy and gene analysis. In addition, skills in parasitology will be gained including maintenance of parasite life cycles and experimental animal work.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a biologically related area. Candidates with experience in parasitology , imaging and/ or with an interest in electron microscopy are encouraged to apply.

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 3 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).

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.

References

Starborg T, O'Sullivan JDB, Carneiro CM, Behnsen J, Else KJ, Grencis RK, Withers PJ (2019) Experimental steering of electron microscopy studies using prior X-ray computed tomography.Ultramicroscopy. 2019 Jun;201:58-67. doi:10.1016/j.ultramic.2019.03.002.
White EC, Houlden A, Bancroft AJ, Hayes KS, Goldrick M, Grencis RK, Roberts IS (2018) Manipulation of host and parasite microbiotas: Survival strategies during chronic nematode infection. Science Advances. 2018 Mar 14;4(3):eaap7399. doi: 10.1126/sciadv.aap7399.
Houlden A, Hayes KS, Bancroft AJ, Worthington JJ, Wang P, Grencis RK, Roberts IS. (2015) Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance. PLoS One.10(5):e0125945. PMID: 25938477.
Foth BJ, Tsai IJ, Reid AJ, Bancroft AJ, Nichol S, Tracey A, Holroyd N, Cotton JA, Stanley EJ, Zarowiecki M, Liu JZ, Huckvale T, Cooper PJ, Grencis RK, Berriman M (2014) Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction. Nature Genetics. 46, 693-700. PMID: 24929830. Hayes, K.S., Bancroft, A.J., Goldrick, M., Portsmouth, C., Roberts I.S.& Grencis, R.K. (2010) Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris: microflora regulates macrofauna. Science. 328, 1391-4. PMID: 20538949.
Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C and Grencis RK (2005) Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science. 308, 1463-1465. PMID: 15933199.

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