| Summary: | Onchocerciasis or river blindness is a major cause of infectious blindness in the world. In severely affected areas, half of the adult population may be blinded by the disease. The human parasite, <i>O.volvulus</i>, is very closely related to the cattle parasite <i>Onchocerca gibsoni</i> which provides an abundant source of biological material for analysis. Thus, <i>O.gibsoni</i> offers a model system for biochemical analysis and drug screening. In these organisms, as in other eukaryotes, microtubules are essential, multifunctional, subcellular components. They are involved in chromosome segregation, cell architecture, motility, intracellular transport, and secretion. The major protein of microtubules is tubulin, a heterodimer of two distinct polypeptides designated α and β. Each subunit has a molecular weight of about 50kD and is encoded by a distinct set of genes. Tubulins are highly conserved proteins and the number of genes coding for both α and β-tubulin vary dramatically between different species. This major structural protein of eukaryotic cells has particular importance in helminthic parasites as it is a target for anthelmintic benzimidazoles, which directly bind to tubulin and inhibit the assembly of microtubules. The effectiveness of such drugs depends on differences in the structure of the tubulin molecules from the parasite and its host. In this context, a genomic library from <i>O.gibsoni</i> has been constructed, screened with a β-tubulin gene from <i>Plasmodium falciparum</i> and the gene isolated. The chromosomal copy of the gene has been completely cloned and sequenced. This has revealed the gene to possess a very complex structure compared to the organisation of all the known β-tubulin genes as the coding region is interrupted by 11 introns. The deduced polypeptide is 444 amino acids long, and its sequence is highly conserved. The position of some introns appear to demarcate functional domains within the protein. The results that have emerged from this thesis are a step forward not only in the rational design of drugs, but also offer an insight into the biology and evolution of an <i>Onchocerca</i> gene and its product.
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