Publication Date

2012

Document Type

Honors Thesis

Department

Biochemistry

Keywords

Nematodes-Genetics, Nematodes-Locomotion, Circadian rhythms, Filariasis-Prevention, Caenorhabditis elegans-Locomotion, C. elegans, Pigment dispersing factor (PDF), Rescue experiment, B. malayi

Abstract

Lymphatic filariasis is a neglected tropical disease which is caused by three parasitic nematodes B. malayi, W. bancrofti and B. timori and currently 1.3 million people in 72 different nations worldwide are endangered of being infected with this disease (1). The major clinical symptoms of elephantiasis and lymphedema are often associated with disability and the disease shows correlation with poverty (30). For this reason the World Health Organization has declared the eradication of lymphatic filariasis a millennium development goal. The currently administered drugs primarily target microfilariae and have shown be only minimal effective against the adult stage worms (42). However, it is this stage of worm which is responsible for the daily production of thousands of microfilariae, which accumulate in the blood causing the previously described symptoms (1). Hence, the identification of potential targets aiming at the interruption of functioning of the adult worms for drug development is an imperative research need. In the parasite B. malayi periodic patterns have been observed in both microfilariae production and microfilariae migration, an aspect which appears to be crucial for the transmission cycle (48, 53). Hence, it is suggested that the organism possesses a network of clock genes maintaining these periodic patterns. In C. elegans pigment dispersing factor (pdf) has been well characterized and has been shown to control both locomotion as well as the oscillation of the circadian clock network (59). This experiment aimed to identify a pdf - like gene in B. malayi and evaluate its function in terms of locomotion by rescuing a loss of locomotion function in mutant pdfr-1 C. elegans animals with the homologous B. malayi cDNA sequence. 2 The initial locomotion analysis of wild-type and mutant C. elegans showed that swimming behavior significantly differs between wild type and the two mutant strains ok3425 and tm4457, which display reduced body bend counts. The remaining locomotion analysis remains to be completed and reassessed by increasing sample size and using more sophisticated locomotion analysis software. Further, parts of the rescue construct have been successfully ligated and the remaining assembly will allow for an assessment of locomotion rescue upon introducing the construct into the C. elegans animals. This thesis project provides groundwork for further progression to identify a potential circadian clock gene in the parasite B. malayi and its effect on locomotion. Upon the assessment of the importance of the gene's role in locomotion in B. malayi, these results would provide a potential target for drug development to fight lymphatic filariasis.

Language

English

Comments

vii, 86 p. : col. ill. Honors project-Smith College, Northampton, Mass., 2012. Includes bibliographical references (p. 81-85)

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