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Researchers take a bite out of bugs
​by Brian WallheimerAgricultures Magazine
Purdue researchers study the genetics of bees as they search for ways to make them less aggressive. Queen bee
The Purdue Bee Laboratory supports entomologists’ research activities. In this hive, workers attend the queen (in the center marked with a circle). Hessian fly
Farmers have battled the Hessian fly since the American Revolution. Through genomics, researchers have shaved decades off the time it will take to discover a solution to controlling the pest. Cate Hill ticks
Catherine Hill has more than her eye on ticks. A medical entomologist, she’s a leading researcher in vector-borne diseases such as Lyme disease. Hill is analyzing the tick genome to understand how the pest transmits Lyme disease.

Bugs have a bad rep—and for good reason.


There’s the gross factor: They’re creepy and crawly and show up in places we don’t want them.


There’s the fear factor: Many of them sting and bite, and often are on us before we even know it.


And there’s the destruction factor: They transmit diseases such as malaria, West Nile virus and Lyme disease, they damage homes and other structures, and they consume crop plants.


But what if we could take away the disease, the ability to hurt crops or transmit disease, or the aggression that leads to stings and bites? Would bees, ticks and flies shed those bad reputations?


Probably not. But Purdue Agriculture researchers are making headway in neutralizing the things that give insects their infamous reputations. While observable results are still likely years away, they’re much closer than they would have been without modern genomics.


“The pest status of the Hessian fly should be reduced in the near future,” Jeff Stuart, an insect molecular geneticist at Purdue, says confidently about the insect that has been a pest of wheat in the United States for more than 200 years. “Genomics is helping us find the mutations that enable the insect to overcome plant resistance, and we expect these discoveries will make resistance more durable.”


Genomics, the study of all of the genetic information contained in an organism, has reduced by years—possibly decades—the time it would take Stuart and his colleagues in the Department of Entomology to reach meaningful results.


Genomics allows scientists to study the entirety of an organism’s genetic code at once, flushing out significant genetic markers and mutations that can give important clues about biological functions.


It has eliminated painstaking searches that previously took years to identify single genes and determine their functions. Scientists would have to identify a gene, knock it out, and then cross the plant or animal that has a muted gene with another plant or animal. The offspring would be observed, and the researcher would try to determine what characteristic was affected by the loss of the target gene.


Handling the Hessian Fly


The Hessian fly is a wheat pest that has evolved to avoid the immunity of the plant and subvert the plant’s biology to its own advantage. It stunts plant growth and causes the plant to transport nutrients directly to the growing larvae feeding behind the leaves.


Wheat plants carrying Hessian fly resistance genes have a higher level of immunity that can defeat the insect. The products of these genes detect the presence of the insect and trigger a plant response that kills invading larvae. However, mutations in Hessian fly genes, called “avirulence genes,” allow the insect to evade even this level of plant immunity. And, as avirulence gene mutations increase in frequency in Hessian fly populations, resistance genes become ineffective as a method of pest control.


“Without the Hessian fly genome sequence, researchers found mutations in two avirulence genes in 10 years,” Stuart says. “With the sequence, we expect we will identify mutations in similar genes more rapidly.”


The speed genomics has brought to insect research has another benefit. Instead of focusing on one aspect of the Hessian fly, Stuart can more easily branch off into other research areas when he finds new vulnerabilities, instead of putting them aside for years while continuing his original search.


Just this year he published findings of an unusual sex chromosome in the fly that divides it into males and two different kinds of females—one that has only male offspring and one that has only female offspring. So, in addition to identifying mutations that allow Hessian flies to attack wheat, Stuart now has the opportunity to investigate this chromosome to determine whether it might be manipulated to influence the fly’s ability to reproduce.


Benevolent Bees


Greg Hunt, a behavioral geneticist, doesn’t want to keep bees from reproducing, but he does want to find out whether it’s possible to make their offspring less aggressive.


For years there have been stories of Africanized “killer” bees moving into North America. Those bees are highly defensive and are likely to sting when disturbed. But European bees are gentler and don’t often sting. “If you cross a bee that stings a lot with a kind that is gentle, you can see how the DNA sorts out in the next generation of bees,” Hunt says.


Hunt has found that crossing aggressive Africanized bees with their gentler European counterparts can make the offspring less aggressive—but not always.


To his surprise, bees that are hybrids between European and Africanized are just as aggressive as the African type when the father is Africanized. But if the father is European, the bees are intermediate in their stinging behavior. “Genetically, these crosses are the same,” Hunt says. “We suppose there’s an epigenetic (change in how gene is expressed) phenomenon going on.”


What that says to Hunt is that genes might be expressed differently based on which parent passes a gene to an offspring. Usually, these sorts of traits are limited in organisms to early embryonic stages, Hunt says, but that’s not what he is seeing in the bees.


The finding has Hunt looking deeper to see if single nucleotide polymorphisms—the building blocks that make up DNA—can be used to measure the expression of genes inherited from the mother or the father.


What Hunt is doing is basic science, far from the stage where his work can be applied to creating gentler bees. But he says it’s one of the most important steps along the path of getting to those observable results.


“How that translates to application is difficult to see right now,” Hunt says. “Even in curing diseases, which people talked about early on, it hasn’t happened yet. But it will. We’re at the trying-tounderstand phase because all of this is still so new. But we’re getting there.”


Hunt compares genomics to a toolbox. The understanding of a particular gene is a tool that goes into that toolbox. When you get enough tools, you can start building. Trying to build before all the tools are there would be like trying to build a house with just a hammer and some nails but no saw, measuring tape or other necessary tools.


Tackling Ticks


Catherine Hill, a Purdue medical entomologist, is using genomics to expand her ticks toolbox. She’s spent more than a year now analyzing the tick’s genome sequence.


Ticks are carriers of Lyme disease, the most common vector-borne disease in the United States, meaning it is transferred via bite from an infected tick to humans and other vertebrates such as rodents, dogs and deer. Lyme disease can cause a rash, fever, chills, body aches and joint swelling. If caught early and treated with antibiotics, the disease can be cured, but in some people, symptoms can linger for years.


Hill hopes new advances can be made through better understanding of the carrier and transmitter of the disease. “We really don’t understand much about ticks and how they transmit Lyme disease at all,” Hill says. “We’re desperate to find new ways to diagnose it or control ticks.”


Hill has been working on understanding how ticks transmit Lyme disease for several years, but getting a genome sequence has opened the door for much quicker analyses of tick genes and their functions.


“It used to be like fishing in the dark. You just dangled a hook out there and hoped to catch something,” Hill says. “I can find the right genes in several months, whereas using the old way—the reverse way—might have taken years.”


Hill says understanding the genome could also lead to better insecticides that could target a tick’s nervous system. The hope is that finding biological functions that are particular only to ticks would lead to the development of insecticides that are deadly to those ticks but not to humans or other organisms.


One of the biggest misconceptions in genomics is that one gene controls a function and that simply eliminating the gene solves the problem. But genes play complicated roles in myriad biological processes that need to be understood first.


It’s not possible to simply find the gene that causes bees to sting. A variety of genes, maybe even a combination, might control the behavioral characteristics that cause a bee to sting.


While Hill says it should take little time to find the genes, understanding the biological processes is what takes time.


“I’ve heard people liken genome sequencing to chopping up a book and then piecing the words into sentences, sentences into paragraphs and paragraphs into pages,” Hill says. “We’re at the sentences-into-paragraphs stage right now.”


It’s those later stages, when scientists are putting paragraphs onto pages, that people might see bees without fearing stings, ticks without fearing Lyme disease and no Hessian flies at all.