University of St Andrews
 
 

Ms Stefanie Menzies
PhD Student

Biomolecular Sciences Building
University of St Andrews
North Haugh
St Andrews
Fife
KY16 9ST
UK

Understanding the Chemistry and Biology of a Novel Class of Natural Product-like Inhibitors of Trypanosomatids

Stefanie is currently on a four-year PhD studentship funded by the Leverhulme Trust and St Andrews 600th Anniversary. Jointly supervised by Prof. Terry Smith and Dr. Gordon Florence.

Her research focuses on drug discovery for Neglected tropical diseases.  Trypanosomatid parasites infect millions of people, causing the diseases African Sleeping Sickness, Chagas Disease and Leishmaniasis. These diseases cause high morbidity and inevitable mortality, and current drug treatments are associated with severe adverse effects and are largely ineffective.   Her primary project is to determine how the natural product chamuvarinin and its derivatives are able to kill these parasites.  To answer this, she has tested a library of analogues against the parasites to establish which structural features of the compounds are important for inhibitory activity, allowing more effective and selective compounds to be synthesized.  Stefanie has shown that the protein target of chamuvarinin is mitochondrial and involved in mitochondrial respiration and is continuing investigations into the exact protein target.  Her secondary project is to investigate the function and essentiality of a novel and unique protein in these parasites, which despite being conserved between all three parasites and absent in humans, has not yet been investigated as a potential drug target. She has shown that the protein is essential to these parasites and is located in the mitochondria.  She is currently establishing an enzyme assay to understand its function and to screen for inhibitors for drug discovery.    

Stefanie studied B.Sc (Hons) Medical Sciences at the University of Leeds, with an honours project in the association between paediatric respiratory syncytial virus infection and development of childhood asthma. She then went on to study M.Sc. Biology and Control of Parasites and Disease Vectors at the Liverpool School of Tropical Medicine. Her Masters dissertation was to investigate whether infection with soil-transmitted helminths increased susceptibility to respiratory virus infection, conducted with Prof. Phil Cooper in rural Ecuador as part of the ongoing cohort study FEPIS (Fundacion Ecuatoriana Para Investigacion en la Salud). After graduating Stefanie continued her work with FEPIS as a research assistant, during which time she was responsible for projects investigating; risk factors for soil-transmitted helminth infections in infants, investigations into the aetiology of non-rotavirus diarrhoea in infants in rural Ecuador, and analysing IgE levels to common Ecuadorian allergens and whether this influenced development of asthma.

Publications

See:

https://www.researchgate.net/profile/Stefanie_Menzies

 

 

Publications

Gould, ER, King, EFB, Menzies, SK, Fraser, AL, Tulloch, LB, Zacharova, MK, Smith, TK & Florence, GJ 2017, 'Simplifying nature: towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins' Bioorganic & Medicinal Chemistry, vol In press. DOI: 10.1016/j.bmc.2017.01.021
Menzies, SK, Tulloch, LB, Florence, GJ & Smith, TK 2016, 'The trypanosome alternative oxidase: a potential drug target?' Parasitology, vol First View. DOI: 10.1017/S0031182016002109
Florence, GJ, Fraser, AL, Gould, ER, King, EF, Menzies, SK, Morris, JC, Thomson, MI, Tulloch, LB, Zacharova, MK & Smith, TK 2016, 'Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors' ChemMedChem, vol 11, no. 14, pp. 1503-1506. DOI: 10.1002/cmdc.201600210
Florence, GJ, Fraser, AL, Gould, ER, King, EFB, Menzies, SK, Morris, JC, Tulloch, LB & Smith, TK 2014, 'Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors' ChemMedChem, vol 9, no. 11, pp. 2548-2556. DOI: 10.1002/cmdc.201402272
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Tel: 01334 463417
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email: unavailable at present
Room: BMS B305



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