Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574872
Title: An investigation into novel helicases from Plasmodium falciparum
Author: Evans, Luke Shaun
Awarding Body: University of Portsmouth
Current Institution: University of Portsmouth
Date of Award: 2012
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Abstract:
With 800 thousand deaths each year resulting from more than 225 million cases of malaria worldwide, the increase of drug-resistant parasites and insecticide-resistant Anopheles gambiae mosquitoes has given rise to the call for new approaches in combating malaria. One proposed strategy focuses on the targeting of Plasmodium helicases due to their necessity in all cellular processes, and therefore the survival of the parasite and the infection of their host. This study describes the novel purification and storage strategies of two Plasmodium falciparum helicases; PFEIF4A (formally PFH45) and PFDH60. This resulted in the yield of relatively large amounts of protein that can be used in high-throughput screening of inhibitors and structural-guided drug design in the future. Moreover, further biochemical and biophysical characterisation has been performed to investigate the specific substrate requirements of each helicase, and the optimal conditions for helicase activity. As well as elucidating information that could provide pathways for specific targeting by both established and novel therapeutic molecules, particularly in the case of PFEIF4A, exposure to temperature just 3 °C above its 37 °C optimum has been shown to have an irreversible and detrimental effect to the proteins activity in vitro. Preliminary experiments into the proteins’ structures have been performed, as well as experiments exploring the effects of a novel DNA-interactive PBD conjugate and the generation and characterisation of aptamers to PFEIF4A. These experiments have contributed to future investigations in to novel anti-malarial therapeutics and diagnostic platforms.
Supervisor: Gowers, Darren Matthew ; Pickford, Andrew Robert ; Callaghan, Anastasia Jane Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Thesis
EThOS ID: uk.bl.ethos.574872  DOI: Not available
Keywords: Biology
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