Invertebrate Automated Phenotyping Platform (INVAPP): An Automated High-Throughput System with Applications in Understanding and Combating Human Diseases

Abstract

The nematode Caenorhabditis elegans is a eukaryotic genetic model organism introduced for studies of animal development and behavior (Brenner S, Genetics 77:71-94, 1974). It is also proving useful to expedite our understanding of human diseases and to explore potential therapies (Ahringer J, Curr Opin Genet Dev 7:410-415, 1997; Culetto E, Sattelle DB, Hum Mol Genet 9:869-877, 2000). Monitoring phenotypic changes and the impact of drug candidates is particularly convenient in the case of C. elegans models of neuromuscular or neurological disorders, where changes in motility and growth are often easily observed and can be conveniently assayed. We therefore developed an Invertebrate Automated Phenotyping Platform (INVAPP) together with an algorithm (Paragon) to facilitate such work (Buckingham SD, Partridge FA, Sattelle DB, Int J Parasitol Drugs Drug Resist Int J Parasitol Drugs Drug Resist 4:226-232, 2014; Partridge FA, Brown AE, Buckingham SD, Willis NJ, Wynne GM, Forman R et al., Int J Parasitol Drugs Drug Resist 8:8-21, 2018). Similarly, in the search for novel chemicals to combat invertebrate pathogens, such as parasitic worms, and disease vectors, such as the mosquito that serves as the malaria parasite vector, the phenotyping of worms and insects in the presence of new candidate drugs and control chemicals (anthelmintics and insecticides) can be extremely useful. This is especially important in view of the current challenges in controlling the malaria vector Anopheles gambiae and the soil-transmitted helminth, the whipworm Trichuris trichiura. For example, the development of resistance to the hitherto highly successful pyrethroid insecticides threatens the impressive gains made by the deployment of insecticide-treated nets (ITNs) and indoor residual sprays (IRS) in reducing malaria cases in the period 2000-2015. Also, there is a need for new anthelmintic drugs to combat soil-transmitted helminths such as whipworm, now that the widely used benzimidazoles are becoming much less effective. In both cases, automated phenotyping assays have a role to play. Here, we describe the use of a simple invertebrate automated phenotyping system and provide some examples that illustrate its utility.

Keywords: Anthelmintic drugs; Automated phenotyping; Chemical screening; Human genetic and infectious diseases; Insecticides.