Biocomputing and Media Research Lab

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Computational Drug Discovery against Onchocerciasis and Filariasis

Description

Filariasis, caused by several nematodes of the superfamily Filarioidea, is one of the seven neglected tropical diseases as defined by the Centers for Disease Control. Diseases in this category affect over one billion people on our planet.

There are several different types of filariasis including subcutaneous, serous cavity, and lymphatic filariasis.  Each form of filariasis is transmitted by blood sucking insects such as mosquitos or flies and cases occur most commonly in tropical areas of Asia, Africa, and Latin America.  Our research focuses on lymphatic filariasis and specifically on brugia malayi as a common agent of infection.

Brugia malayi is a nematode that affects the lymphatic system. The worm's offspring or microfilariae enter the blood stream and are transmitted when a mosquito ingests the infected blood. The microfilariae reach their infective stage inside the mosquito and then infect a human or animal once bitten by the mosquito. The adult worms live in the lymph nodes and as they die, molt, or the females produce micofilariae the host's symptoms worsen. Early symptoms include fever and tender lymph nodes but can escalate to elephantiasis (swelling and enlargement of the limbs) caused by blockage in the lymphatic system.

The goal of our research is to develop novel screening technologies that can be used in high-throughput settings to screen hundreds of thousands of molecules to identify drug candidates for further optimization. Our approach is based on developing a framework, which we call "computational phenomics". In this framework, the phenotypes exhibited by the parasite as a response to different drugs, are captured using digital imaging and computationally quantified to establish structure-activity (phenotype) relationships.


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