The CRISPR gene editing creates a wave of exotic model organisms

Joseph Parker wanted to know what ticked beetle since the age of seven. The entomologist has spent decades collecting and observing insects, some of whom live among ants and feed on their larvae. But without tools to study the genetic and cerebral mechanisms underlying beetle behavior, Parker focused his doctoral thesis on Drosophila fruit flies – an established model organism.

More than a decade later, the advent of the CRISPR gene modification technique made Parker's dream come true. It uses CRISPR to study symbiosis in bark beetles (Staphylinidae) in his laboratory at the California Institute of Technology in Pasadena. By eliminating the genes in the beetles that live with the ants and in those who do not, Parker hopes to understand how the DNA of the insect has changed while their lifestyles diverge. "We design a model system out of nothing," he says.

Biologists have recognized the ability of CRISPR to rapidly and inexpensively modify the genomes of popular model organisms, such as mice, fruit flies and monkeys. Now they are trying the tool on more exotic species, many of which have never been bred in the lab or their genomes analyzed. "We are finally ready to start developing what we call a model organism," said Tessa Montague, a molecular biologist at Columbia University in New York.

Montague works on Hawaiian squid (Scope of Euprymna) and dwarf cuttlefish (Sepia bandensis), whose unusual camouflage acts as an outward display of their brain activity. Cephalopods project patterns on their skin to match what they see around them. But it has been difficult to know how their brain processes stimuli. Researchers would normally proceed by incorporating electrodes or other sensors into the skull – but squid and cuttlefish are boned.

Last year, Montague and his colleagues successfully injected CRISPR components into twisted cuttlefish and squid embryos for the first time. Now, they are trying to genetically modify cephalopod neurons to light up when they fire up.

Technical KO

Other researchers use CRISPR to study the distinctive social behaviors of species. Daniel Kronauer, a biologist at Rockefeller University in New York, has created ants raider (Ooceraea biroi) who can not smell the pheromones. In experiments, genetically modified ants could not maintain the complex hierarchy observed in a normal ant raider colony¹. Scientists are now using CRISPR to modify genes thought to influence the behavior of plundering ants.

Then there are species that threaten human health or the environment – like the pea aphid (Acyrthosphion pisum), an insect that attacks legumes worldwide. To modify the aphid genome with CRISPR, a team led by Shuji Shigenobu, an evolution geneticist at the National Institute of Fundamental Biology in Okazaki, Japan, had to manipulate the complex life cycle of this insect. Aphids born in summer reproduce asexually, by cloning, while those born in autumn lay eggs.

The Shigenobu team set up an incubator simulating cool temperatures and the short days of autumn so that its aphids lay eggs that scientists could inject with CRISPR components.

After four years, the team managed to publish a pigment gene as proof of concept, Shigenobu announced last month at a conference held at the Howard Hughes Medical Institute Janelia Research Campus in Ashburn, Virginia. He hopes that by modifying other parts of the aphid genome, researchers will be able to learn more about how insects interact with plants. This information could lead to the production of better pesticides.

Forward

Developing animal models requires a lot of time and money, and until recently, there was little support for this type of work. In 2016, the US National Science Foundation launched a $ 24 million program to create model organisms and in doing so reveal the genetic and molecular mechanisms underlying complex traits and behaviors.

The program supports research to develop tools to probe species genomes, study the life cycle of organisms, and develop protocols for raising these species in the laboratory. This support has begun to bear fruit: in March, for example, researchers at the University of Georgia in Athens said:² that they used CRISPR to create the first genetically modified reptile, the brown anole (Anolis sagrei).

Despite such promising early results, the desire to create model organisms with CRISPR has revealed how little is known about the genome, life cycle and habits of many species. Researchers face practical challenges, such as determining how to inject CRISPR components into embryos and convincing capricious and fragile species to reproduce in the laboratory.

"The reason that classical model systems have been chosen is that they are fundamentally harmful. Nothing can stop them from growing up, "says Montague. "But if we take on the challenge of working on new organizations because they have amazing functionality, they are often not happy to develop under [just] all the conditions. "

This has forced scientists to evaluate the efforts required to study a particular trait in relation to the potential benefits. Genome modification requires a thorough understanding of a species' behavior and life cycle – a daunting challenge when it is only studied by a handful of people around the world. "People do not choose these model systems lightly," says David Stern, biologist at Janelia.

Stern knows it very well: he and his colleagues managed to create a fruit fly species only after discovering that the insects needed an olfactory signal to lay their eggs – the smell of a particular chemical made by plants.

Nevertheless, researchers' interest in the development of atypical animal models continues to grow. Montague and his colleagues have created a tool called CHOPCHOP, which allows them to design a CRISPR system to edit specific genes in any DNA extract. Until now, scientists have sent him genetic sequences of more than 200 different species, including plants, fungi, viruses and farm animals.

"I had this weekly reminder that these molecular tools work in just about every organism on the planet," says Montague. "It's such an exciting time to work on any model organism – especially these new and strange creatures."