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Title: Molecular studies on signal transduction in Plasmodium falciparum
Author: Sultan, Ali Awad ElKarim M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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The research outlined in this thesis was primarily designed to study certain genes and their encoded proteins which regulate the development of the malaria parasite, Plasmodium falciparum, through its intra-erythrocytic life cycle. The work has involved molecular cloning and characterisation of a P. falciparum homologue of the ras-related nuclear GTP-binding protein, Ran/TC4. This protein has been shown to play a key role in control of the cell cycle in mammalian and yeast systems. In this work, the homologous P. falciparum gene, pfran, has been cloned and characterised. Its predicted protein product is 214 amino acids long and contains consensus motifs found in the Ras superfamily. The expression of a 1.5 kb pfran transcript has been found to change during the cell cycle, reaching a peak at the trophozoite and schizont stages. Western blotting and immunoprecipitation using a polyclonal antiserum raised against the expressed protein have shown that pfran encodes a protein 27 kDa in size. Immunofluorescence assays have shown that pfran is localised in both the nucleus and cytoplasm of the parasite. Some experiments were undertaken to express pfran in yeast which had only limited success. Ran/TC4 is proposed to function in conjunction with the chromatin-binding protein RCC1, (Regulator of the Chromosome Condensation -1), to couple the completion of DNA synthesis with initiation of mitosis. This takes place by the activation of a cyclin-p34 CDC2 complex. To understand better the regulation of the cell cycle in malaria parasites, and the role of Ran in this process, the p. falciparum homologue of the RCC1 has been cloned and partially sequenced. Expression of this gene and its possible association with pfran have been studied. The implications of these findings are discussed in the thesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available