SA01: Developing new treatments for the blinding protozoan eye infection Acanthamoeba keratitis

Supervisory Team

Dr Wayne Heaselgrave, School of Biomedical Science and Physiology and Dr Daniel Keddie, School of Biology, Chemistry and Forensic Science

Project Description

Acanthamoeba is a free-living amoeba that can found in virtually all soil and water habitats throughout the world. Acanthamoeba lives in all of our homes and can be isolated from kitchen/bathroom taps, showerheads, vacuum cleaner dust and garden soil. The organism usually feeds bacteria but is an opportunistic pathogen of humans causing a fatal encephalitis in immunocompromised patients as well as a blinding infection of the eye called Acanthamoeba keratitis (AK).

AK is usually found in contact lens wearers and occurs through poor hygiene practices which include sleeping in lenses, storing lenses in tap water and not disinfecting lenses properly. In the UK there are approximately 5 million contact lens and approximately 200 cases of the infection each year. What is particularly worrying about this infection is that there is currently no licenced treatment. An unlicensed treatment does exist which includes the swimming pool disinfectant polyhexamethylene biguanide (PHMB). However, many patients particularly those diagnosed late do not respond to the treatment and suffer irreversible destruction of the corneal tissue requiring repeated corneal transplantation and eventually surgical removal of the eye.

Therefore there is an urgent need to identify new treatments and drug targets for this infection. Compounds including triazoles, biguanides, diamidines and amidoamines have previously demonstrated activity against Acanthamoeba. This proposal will involve the synthesis of novel compounds from the above classes to be tested against trophozoites and cysts of Acanthamoeba. Testing will utilise a high throughput screening assay and the best candidate compounds for further development will be identified by analysing the structure activity relationships (SAR) of the compounds

References

Heaselgrave W, Kilvington S. The Characterisation of an Adrenergic Signalling System Involved in the Encystment of the Ocular Pathogen Acanthamoeba spp. J Eukaryot Microbiol. 2016 Sep;63(5):629-34.

Eligibility

We welcome applications at any time from self-funded students that are well qualified and highly motivated. Applicants should have a recognised Honours or Masters Degree with a 2.1 or equivalent in Microbiology (or a related field). Applicants whose entry award was not delivered in English, or non-native speaker of English shall be required to demonstrate proficiency in English at least to the level of an IELTS score of 7.0 or its equivalent.

How to apply

Complete the Research Project Application Form (Word doc 679k) and email to RIHS@wlv.ac.uk.

See Guidance for the Completion of the Research Project Application Form (Word doc 23k) for details.

For more information

For an informal discussion please contact Dr Heaselgrave or Dr Keddie via email at w.heaselgrave@wlv.ac.uk  or d.keddie@wlv.ac.uk.