Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique

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Ding, Xianting
Njus, Zach
Kong, Taejoon
Su, Wenqiong
Ho, Chih-Ming
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American Association for the Advancement of Science
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Electrical and Computer Engineering

The Department of Electrical and Computer Engineering (ECpE) contains two focuses. The focus on Electrical Engineering teaches students in the fields of control systems, electromagnetics and non-destructive evaluation, microelectronics, electric power & energy systems, and the like. The Computer Engineering focus teaches in the fields of software systems, embedded systems, networking, information security, computer architecture, etc.

The Department of Electrical Engineering was formed in 1909 from the division of the Department of Physics and Electrical Engineering. In 1985 its name changed to Department of Electrical Engineering and Computer Engineering. In 1995 it became the Department of Electrical and Computer Engineering.

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  • Department of Electrical Engineering (1909-1985)
  • Department of Electrical Engineering and Computer Engineering (1985-1995)

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Infections from parasitic nematodes (or roundworms) contribute to a significant disease burden and productivity losses for humans and livestock. The limited number of anthelmintics (or antinematode drugs) available today to treat these infections are rapidly losing their efficacy as multidrug resistance in parasites becomes a global health challenge. We propose an engineering approach to discover an anthelmintic drug combination that is more potent at killing wild-type Caenorhabditis elegans worms than four individual drugs. In the experiment, freely swimming single worms are enclosed in microfluidic drug environments to assess the centroid velocity and track curvature of worm movements. After analyzing the behavioral data in every iteration, the feedback system control (FSC) scheme is used to predict new drug combinations to test. Through a differential evolutionary search, the winning drug combination is reached that produces minimal centroid velocity and high track curvature, while requiring each drug in less than their EC50 concentrations. The FSC approach is model-less and does not need any information on the drug pharmacology, signaling pathways, or animal biology. Toward combating multidrug resistance, the method presented here is applicable to the discovery of new potent combinations of available anthelmintics on C. elegans, parasitic nematodes, and other small model organisms.
This article is published as Ding, Xianting, Zach Njus, Taejoon Kong, Wenqiong Su, Chih-Ming Ho, and Santosh Pandey. "Effective drug combination for Caenorhabditis elegans nematodes discovered by output-driven feedback system control technique." Science Advances 3, no. 10 (2017): eaao1254. DOI: 10.1126/sciadv.aao1254. Copyright 2017 The Authors. Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Posted with permission.