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New grant to study fish genomics, behavior

BY Kathryne Metcalf.

The three-spined stickleback is a funny sort of a fish. They’re somewhat non-distinct: drabbish silver, small, and minnow-like, native to salt- and freshwater bodies throughout most of the Northern hemisphere. However, different stickleback populations have evolved very distinct morphological traits, demonstrating a natural diversity that makes them an ideal candidate in which to examine the mechanics of adaptive evolution and ecology. More strikingly, they display a wide number of behaviors related to breeding, territorial disputes, and foraging that make them fascinating models for the study of animal behavior, particularly as to how genomics can both influence and be influenced by social dynamics.

A new grant through the National Science Foundation’s Enabling Discovery through GEnomic Tools (EDGE) program promises to expand our knowledge of this foundational fish species. The $1.7 million dollar, three year award is led by Principal Investigator and biologist Daniel Bolnick (University of Texas at Austin), and supported by four additional co-PIs including biologists Alison Bell (University of Illinois Urbana-Champaign) and Katherine Milligan-Myhre (University of Alaska Anchorage) and geneticists Craig Miller (University of California, Berkeley) and Michael White (University of Georgia).

To improve tools and techniques in the broader stickleback research community, the team has opted for a multi-pronged approach: they aim to develop new strategies for genetic manipulation that will make decoding the already-sequenced fish genome easier to decipher, develop stock lines that will enable researchers to better standardize and replicate experiments, and create training tools to benefit the 100+ labs working on stickleback research worldwide.

To Bell and graduate student Noelle James, the stickleback represents a behavioral mystery: though previous research has made it clear their genetic makeup and behavior are closely linked, it remains unclear what direction the causation flows—does behavior change subsequent gene expression, or does gene expression shape behavior?

“Right now, we have no way of trying to link changes in gene expression to changes in behavior. We don’t know the direction of the causality,” explains Bell. “But a great way to get around that would be to manipulate the gene itself, so then if you see a change in behavior you can make a stronger argument that changes in the expression of the gene caused it.”

Previous research at the IGB has found that honey bees, sticklebacks and mice share some behaviorally-linked genes that are active in both species for up to two hours following an aggressive encounter, such as being confronted by an “intruder” into the animal’s territory. Now, Bell and James want to see how those same genes function in stickleback by performing what’s known as a “knockdown study,” which modifies expression in the organism to silence specific genes.

Currently, genetic modification in sticklebacks has only been performed during embryonic developmental stages; but because the genes implicated in behavioral outcomes also control aspects of development, changing their expression in an embryo would likely be fatal. By using a modified virus to transfer genetic material to the fish brain, Bell and James believe they can observe behavioral effects without impacting other functions.

“We study behaviors that are natural, not lab induced,” says James. “So to do this, we work with wild-caught adult fish…animals that have had a natural rearing environment and have grown up normally, and we try to change expression there. That’s the biggest challenge for us, changing expression in the adult, which has never been done in sticklebacks before.”

In all, the team supported by the EDGE grant hopes to clarify genetic causation in multiple correlated areas: where Bell’s lab is focused on behavior, others are examining host-parasite and host-microbe interactions, evolution, ecological genetics, and more. They believe that in the process of developing needed tools to address their own specific research aims, they can simultaneously improve the tools and techniques used to study sticklebacks in the broader research community, benefiting labs worldwide.

“While we’re developing [genetic tools] for adult sticklebacks to study behavior, they could be used by any other lab to study other genes,” said James. “That’s one of our big goals.”

The EDGE program, administered by NSF’s Biological Sciences Directorate, funds projects that work to develop new genomic tools and provide the research community with information about how to use them. EDGE-funded projects move the scientific community closer to being able to predict phenotype by developing enhanced genomic tools and infrastructure.

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