Designing More Benign Bugs
UK research duo controlling insect growth
When, at exactly 2 a.m. on a warm spring night in 1997, Davy Jones finally got the lab results he'd been hoping for, he was so excited he phoned his wife and research partner, Grace, and woke her out of a deep sleep. Was she upset about this untimely awakening?
"No! I was ecstatic," Grace says. "I jumped out of bed and threw on a jacket and ran to the lab."
Davy Jones, a professor of toxicology, and Grace Jones, a professor of biology, are working to control insect development.
What they had detected was the elusive result of a receptor binding to something called juvenile hormone, a substance that controls insect development and metamorphosis. "Before I called Grace and shouted 'Eureka' into her ear, I repeated the experiment to make sure it worked. It did. It was an absolute rush." And when Grace joined him in the lab, they tried the experiment a third time. Again it worked, and they were able to celebrate this Eureka moment together.
The two had been on sabbatical, working in exhausting 12-hour shifts at Rockefeller University in New York, where they chose to go, Davy says, because of the "environment of experts" there in gene biochemistry. The Joneses' goal was to find out how juvenile hormone binds, or doesn’t bind (chemically adhere), to specific receptors. At Rockefeller, the two continued experiments that Grace had recently begun at the Massachusetts Institute of Technology in the lab of Kentucky native and Nobel Prize-winner Phil Sharp.
Juvenile hormone gets its name from the fact that it causes the immature insect, such as the caterpillar, to remain in that stage instead of further developing to the adult stagesthe moth or the butterfly. The goal of this work was to understand and be able to regulate insect growth.
As any gardener knows, a gang of caterpillars can eat vegetables right down to the ground. Left to their own ravenous devices, the insects can eat all the leaves off large branches or small trees. "So we don't want the caterpillar to stay in this juvenile stage," says Grace. "We'd want it to develop as quickly as possible to adulthood and become a moth because moths don't eat plants."
Davy adds that with some other insects, the opposite growth pattern would be desirable. "We'd want the mosquito to stay in the juvenile stage and not advance to become the adult blood-sucker we dodge and swat."
The Joneses knew that insecticides based on their discovery could do either of these two things: accelerate or retard insect growth. "Rather than a broad spectrum pesticide, we wanted to find a selective 'magic bullet' that would stop the insect growth at the right stage but that wouldn't be toxic to humans and wildlifesomething that wouldn't toxify the environment," Davy says.
Finding this magic bullet wasn't easy. A major challenge was to break through a scientific bottleneck in insect hormone researchto discover which protein receptors become activated when they interact with juvenile hormone. The physiological properties of juvenile hormone are well established, but finding the receptors that convert these properties had been like trying to fit a plug into an outlet in a pitch-black airplane hangar.
About six years ago, the research team decided to try a new technology that had not been utilized before in the insect hormone field, Davy explains. They enlisted the aid of an amino acid component of proteins called tryptophan, which has the useful property of giving off fluorescent light when excited; but that fluorescence is disturbed if another chemical compound is bound nearby.
He and Grace identified a possible receptor they thought might bind juvenile hormone, and luckily this receptor has a naturally occurring tryptophan right next to where the hormone would bind. Tryptophan, they reasoned, could literally light the way to their hoped-for results.
"We envisioned that if juvenile hormone bound to this receptor, then we could detect that binding by its effect to disturb the fluorescence of the receptor," Davy says. "And this is exactly the case."
These results have generated two NIH grants and one NSF grant, a total of nearly $2 million that has funded their further exploration and refinement of this process. And UK has supported a patent application of the fluorescence technology.
As the Joneses worked to unravel the receptor mystery, they were confronted with a different, personal challenge. In August 2000, Grace suffered a severe stroke that left her body paralyzed on one side, severely limiting her mobility. In the foreseeable future Grace wouldn't be hustling back and forth between her lab and her husband's lab over at the medical center, which had for so long been her trademark style.
"It was great how at this point the department stepped up to help," Grace says. "Chuck Staben, our chairperson, went out of his way to make it possible for Davy to move his lab to the biology building, right across the hallway from me."
Grace says her stroke has had one silver lining: it has brought home to her how important it is to understand how hormones stimulate the differentiation of cells into particular tissues. "A major limitation in the treatment of stroke or brain injury is a lack of understanding of how to stimulate regrowth of nerve tissue or how to direct stem cells to grow and replace injured nerve cells. If I can help the basic understanding of cellular differentation in a way that eventually contributes to medical treatments that help other stroke sufferers 'metamorphose' back to their healthy state, that will be my most meaningful Eureka moment."