Publication Date

2014

Document Type

Honors Thesis

Department

Biological Sciences

Keywords

Circadian rhythms, Evolution, Parasites, Pigments (Biology), Cycles, Genomics, Caenorhabditis elegans., Circadian, Period, Pigment dispersing factor, Periodicity, Comparative genomics, C. elegans, Brugia malayi

Abstract

Lymphatic filariasis is one the World Health Organization's "Big Seven" neglected tropical diseases which currently affects 120 million people across 73 endemic nations1. The primary clinical manifestations of lymphatic filariasis include elephantiasis and severe lymphedema that trigger permanent deformation and disability of the afflicted tissues21. Permanent disability consequentially perpetuates chronic poverty, and has prompted the World Health Organization to set disease elimination as a Millennium Development Goal21,23. Current treatment regimens are ineffective against the infective third-stage larvae and the reproductively active adult parasites21,24. Thus, an increased need exists for anti-helminthic therapies that can either kill microfilariae, third-stage larvae, or disrupt transmission and reproductive behavior. The filarial nematode Brugia malayi, responsible for 10 % of all reported cases, exhibits periodic patterning in both adult female egg-laying, and microfilariae movement that has yet to be examined by molecular methods8, 29. Both behaviors are deemed critical for effective parasite transmission, and appear to be entrained to a consistent 24-hour patterning. Because underlying molecular regulators of such behaviors have been identified in a diverse range of phyla, we suggest that a conserved molecular network regulates the observed circadian periodicity of B. malayi transmission and reproduction. We have thus far identified, by use of comparative genomics, two major circadian clock gene candidates that may participate in B. malayi periodicity. These were identified by similarity to well-documented Caenorhabdiditis elegans clock genes. We have experimentally amplified these gene sequences, and generated bacterial constructs that will be used for phenotypic assessment of B. malayi candidate protein function following generation of C. elegans transgenic lines. This thesis lays the foundation for further research to molecularly characterize clock gene functionality in B. malayi.

Language

English

Comments

106 pages : illustrations (some color). Honors Project-Smith College, 2014. Includes bibliographical references (pages 97-102)

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