Biological Science, University of the West of Scotland
Tenure since 2017
Quaternary Ammonium Compounds (QACs) biodegradation pathway in Acanthamoeba castellanii as a model for understanding drug resistance
Treatment of the eye disease Acanthamoeba keratitis (AK) caused by the protozoan parasite Acanthamoeba, is hampered by the ability of the protist to alternate rapidly between the infective vegetative trophozoite and protective cyst life cycle forms. Cysts are unaffected by chemical attack and their reversion to trophozoites when conditions become favourable is the main cause of relapse in AK sufferers. Consequently, this has increased the incidence rates of AK, particularly amongst contact lens wearers. The financial and emotional costs of sight loss from AK to the National Health Service (NHS) and the individual respectively is high and this calls for the development of new curative compounds for AK or disinfectants to sterilise contact lenses between use.
During my undergraduate degree, I have shown that quaternary ammonium compounds (QACs), particularly analogues with long alkyl carbon chains were effective against Acanthamoeba trophozoites and cysts, producing death by DNA damage and leakage after pore formation on the plasma membrane. In contrast, QACs with short alkyl carbon chains had no anti-amoeboid activity and feeding experiments showed that they increased intracellular ammonium levels and cell density in vitro. It was postulated that the enzymatic activities of the two families of amine oxidases present in the gene content of this parasite degraded QACs to ammonium and thus it is possible for the over-expression of these enzymes to result in the degradation of QACs with longer chains leading to the parasite developing resistance against them if used inappropriately. In my proposed study these postulations will be investigated using multiple but complimentary approaches which include recombinant protein technology and enzymatic assays. Further, a systems biological approach will be used to analyse the metabolome of parasites over-expressing amine oxidase or parasites with induced QAC resistance under controlled conditions. It is anticipated that the results obtained will identify the role of amine oxidases in QAC degradation and the route taken by the parasite to develop resistance to them. Potential biomarkers for identifying resistant parasites in the community will also be identified. This project provides an excellent opportunity to validate the use of QACs as a disinfectant for contact lens cleansing and will aid the chemo-surveillance of QAC-resistant parasites during routine use.
I graduated from the University of the West of Scotland with a First Class Honours degree in Applied Bioscience and Zoology in 2017. During my degree, I spent my breaks working in research labs at UWS working on various projects including carrying out my research on the parasitic protozoa, Acanthamoeba under the supervision of Dr Roderick Williams, which was sponsored by the Carnegie Trust Undergraduate Vacation Scholarship. Also, under the Scottish Government-UWS Outward Mobility Fund Project, I was selected to visit the University of Wisconsin, Platteville to observe learning and teaching strategies employed in Higher Education Intuitions (HEIs) in the United States for comparison to that of the HEIs in the UK. I have during my time at UWS received several awards of merit which include the UWS Court Medal for academic excellence for my year in 2015/2016 and 2016/2017, the Royal Society of Biology Award for top performing biology student and the Dr William J. C. Watt Medal for the most distinguished science student.