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Development of a three dimensional in vitro model of the human cornea to dissect the inflammatory events associated with sight-threatening ocular pathogens


Project Description

The presence of microbes at the corneal surface may trigger low grade discomfort through to acute eye infection and permanent loss of vision. The molecular events underlying the inflammatory response associated with colonisation of these tissues with specific microbes remain unclear; understanding these events may uncover new targets for pharmaceutical intervention. We will establish and validate a corneal epithelial model system making use of our expertise in collagen gel tissue modelling (enabling us to replicate stromal epithelial tissue), and additionally using corneal epithelial cells cultures (grown as multilayer cultures).

This model will then be exposed to live bacteria and / or bacterial toxins from different bacterial species, and the cellular response assessed by proteomic analysis for production of cytokines and other pro-inflammatory signals. Additionally we will obtain tear samples from the clinic and compare the inflammatory response associated with specific colonising organisms with that uncovered after introduction of the same organisms to our model system.

The model would ultimately be useful in screening novel antimicrobial formulations to tailor activity towards those organisms with the strongest pro-inflammatory effect.

This is an opportunity to work with two award-winning and well-funded University of Manchester research groups, on a project with potential to have direct real-world impact.

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. 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.

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).

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

Bakkar MM, Hardaker L, March P, Morgan PB, Maldonado-Codina C, Dobson CB. The cellular basis for biocide-induced fluorescein hyperfluorescence in mammalian cell culture. PLoS ONE 2014;9.

Forbes S, McBain AJ, Felton-Smith S, Jowitt TA, Birchenough HL, Dobson CB. Comparative surface antimicrobial properties of synthetic biocides and novel human apolipoprotein E derived antimicrobial peptides. Biomaterials 2013;34:5453–64.

Maldonado-Codina C, Read ML, Efron N, Dobson CB, Morgan PB. Observation of solution-induced corneal staining with fluorescein, rose bengal and lissamine green. Cont Lens Anterior Eye 2013.

Wright EA, Payne KAP, Jowitt TA, Howard M, Morgan PB, Maldonado-Codina C, et al. Preservation of human tear protein structure and function by a novel contact lens multipurpose solution containing protein-stabilizing agents. Eye Contact Lens 2012;38:36–42.

Werthén M, Henriksson L, Jensen PØ, Sternberg C, Givskov M, Bjarnsholt T. An in vitro model of bacterial infections in wounds and other soft tissues. Apmis 2010;118:156–64

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