Host Manipulation, Gene Editing, and Non-Traditional Model Organisms: A New Frontier for Behavioral Research?

Abstract

Insects and parasites dominate the biosphere, in terms of known biodiversity and mode of life, respectively. Consequently, insects play a part in many host-parasite systems, either as parasite, host, or both. Moreover, a lot of these systems involve adaptive parasite-induced changes of host phenotype (typically behavior or morphology), which is commonly known as host manipulation. While many host manipulation systems have been described within the last few decades, the proximate mechanisms that underpin host phenotypic change are still largely unknown. Given the intimate co-evolutionary history of host-parasite systems, teasing apart the intricate network of biochemical reactions involved in host manipulation requires the integration of various complementary technologies. In this perspective, we stress the importance of multidisciplinary research on host manipulation, such as high-throughput sequencing methods (genomics and transcriptomics) to search for candidate mechanisms that are activated during a manipulation event. Then, we argue that gene editing technologies, specifically the CRISPR-Cas9 system, are a powerful way to test for the functional roles of candidate mechanisms, in both the parasite and the host. Finally, given the sheer diversity of unique host-parasite systems discovered to date, there is indeed a tremendous potential to create novel non-traditional model systems that could greatly expand our capacity to test the fundamental aspects of behavior and behavioral regulation.

Keywords: CRISPR-Cas9; behavior; gene editing; host manipulation; insect; non-traditional model organism.

Figure 1

Depicting the multidimensional nature of host manipulation in insects. A parasite produces “manipulation factor(s)” that can interact with and cause cascading effects in various host biological systems, such as the nervous and immune systems. These manipulation factor(s) can impact the host at one or more levels of biological organization (dashed rectangle), from the genome to the proteome. These interactions ultimately result in adaptive changes in host external phenotype (typically behavior or morphology) that benefit the parasite. Note that the parasite was haphazardly placed inside the insect; its location varies with each system and can play an important role during manipulation. Figure inspired by Hébert and Aubin-Horth (37) and Herbison (38).

Figure 2

Simplified depiction of how loss-of-function CRISPR-Cas9 gene editing can be used to elucidate the proximate mechanisms of host manipulation. (A) During a natural manipulation event, “manipulation factor(s)”, encoded in the parasite genome, are released into the host. These factors initiate a series of host-parasite interactions that impact one or more host mechanisms encoded in the host genome, resulting in external changes in host phenotype (typically behavior or morphology). (B) CRISPR-Cas9 is used on a living parasite to knockout a candidate parasite gene with potential manipulation functions, allowing researchers to test which parasite genes have a functional role during manipulation. (C) CRISPR-Cas9 is used on a living host to knockout a candidate gene potentially manipulated by the parasite, allowing researchers to test which host mechanisms underlie the altered phenotype.