Academic journal article Genetics

Rendering the Intractable More Tractable: Tools from Caenorhabditis Elegans Ripe for Import into Parasitic Nematodes

Academic journal article Genetics

Rendering the Intractable More Tractable: Tools from Caenorhabditis Elegans Ripe for Import into Parasitic Nematodes

Article excerpt

CAENORHABDITIS ELEGANS has been a flagship model organism for over 40 years, and the research community has harnessed it to explore a wide range of biological questions, including but not limited to cell death, developmental timing, genome defense, neurobiology, and aging. The value of C. elegans as a model was not diminished by the lack of genetic tools. However, recent technological advances that enable genome editing, transcriptional and translational manipulation, in vivo labeling, and cell-specific proteomics have opened new avenues of investigation. Thanks to significant investment of time and resources, C. elegans now has an extensive toolkit to facilitate these studies.

In recent years, the global health burden of parasitic nematodes has gained wide attention, as they infect over a billion people (Hotez et al. 2008; Lustigman et al. 2012). Infection is rarely fatal, but those who are infected can suffer from debilitating symptoms. Helminth infection depresses human health, cognition, and productivity, and increases the severity of other common diseases caused by viruses and bacterial pathogens including HIV, malaria, and tuberculosis (Hotez et al. 2008; Lustigman et al. 2012). Furthermore, nematodes also parasitize crops and livestock, causing huge losses in production (Jones et al. 2013; Roeber et al. 2013). The World Health Organization (WHO) has listed certain parasite infections as targets for eradication by the year 2020 (ITFDE 2008; Boatin et al. 2012; Keenan et al. 2013). Efforts to define eradication strategies can be challenging; many parasites have intricate lifecycles with specific host and vector requirements, which in contrast to C. elegans, has limited the types of molecular analyses that can be performed. Recognizing the urgency and scope of these issues, both the C. elegans and the parasitic nematode communities have responded by bringing together the expertise and knowledge of their respective organisms; at two recent international C. elegans meetings, there were workshops to bridge the divide between C. elegans researchers and parasitologists. Furthermore, additional funding opportunities have been created, such as the Faucett Catalyst grant in 2013.

In this "toolbox" review I will: (i) outline the state of technology in several commonly studied parasitic nematodes, which could be employed by C. elegans researchers looking to translate their findings into a biomedically relevant parasite; (ii) highlight tools from C. elegans that could be valuable to parasitologists; and (iii) briefly discuss research areas that can be opened by developing these tools. I will focus on two technologies: fluorescent reporters and the CRISPR/ Cas9 system for genome editing.

Lessons Learned from Import into Nonparasites

Beautiful evolution-development and population genetics research has come from using C. elegans, related Caenorhabditis species, and other nonparasitic nematodes such as Pristionchus pacificus. A major impediment to advancing these studies was the lack of genetic tools in these nonparasitic species. It is therefore instructive to examine the barriers faced by researchers seeking to develop C. briggsae and other nonparasitic species as genetic models. Hindsight allows for the identification of particularly successful adaptations, informing fruitful lines of inquiry.

Wei et al. (2014) astutely noted that it typically takes years to build a collection of tools, even those as basic as isolated marker mutations and genetic balancers. Bioinformatic resources such as an annotated genome sequence and single nucleotide polymorphism maps were key in driving development of C. briggsae as a genetic model. The acquisition of a Cbr-unc-119 mutation from a genetic screen provided a selectable marker to permit ballistic transformation and generation of fluorescent reporter strains (Zhao et al. 2010). Similarly, P. pacificus has a sequenced genome and a well-developed toolkit consisting of forward genetic approaches and DNA transformation (Hong and Sommer 2006; Dieterich et al. …

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