Publication Date

2012

Document Type

Honors Thesis

Department

Biochemistry

Keywords

Nematodes-Genetics, Thioredoxin, Peroxidase, Filariasis-Prevention, Elephantiasis, Lymphatic filariasis, Brugi malayi, Splice leader addition site, Promoter, tpx-2, Thioredoxin peroxidase gene

Abstract

Lymphatic filariasis is a Neglected Tropical Disease which afflicts 120 million people worldwide, putting more than one billion people at risk of infection (CDC, 2010). The causative agents for lymphatic filariasis are Wuchereria bancrofti, Brugia malayi, and Brugia timori. Severe infections can lead to elephantiasis, lymphoedema, hydrocele, chyluria, tropical pulmonary eosinophilia, adenopathy, haematuria, to name a few (Addiss, D.G., and Brady, M.A., 2007; Dreyer, Dreyer, and Piessens, 1999). These symptoms are often associated with disfiguring physical appearance and chronic pains, causing a burden on the patients and a loss of the labor force worldwide. Therefore, in 2010, the World Health Organization had launched a program to eradicate the disease as a public health problem by 2020 (WHO, 2010). Although Brugia malayi only causes 10% of lymphatic filariasis infection, they are the ideal model to use in laboratory investigation because all five stages of B. malayi life cycle can be cultured in lab (Williams, 1999). The L3 stage when the parasite first changes its host from the mosquito to the human body was proposed to be a target for parasitic elimination when they are still vulnerable and exist in a small number. To target the L3 stage, thioredoxin peroxidase-2 gene (essential gene for the parasite's defense against the human host immune system) was investigated for possible mechanisms to turn this gene off, one of which was the manipulation of the tpx-2 promoter. Mutation of the region from -436 to -430 nucleotides upstream of the start codon of Bm-tpx-2, caused almost 100% loss of promoter activity. This result gives ways for further investigation of associated transcription factors, which can serve as potential drug and vaccine targets.

Language

English

Comments

111 p. : col. ill. Honors project-Smith College, Northampton, Mass., 2012. Includes bibliographical references (p. 101-111)

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