Black-legged ticks in forests of the Northeast and Midwest have a variety of options for the three blood meals they consume in their lifetime: In their earlier stages, the ticks feed on at least 41 species of mammals, from chipmunks to black bears, plus 57 species of birds and 14 species of lizards. In adulthood, they will hop onto at least 27 species of mammals and one type of lizard.

These are the ticks that transmit pathogens that are harmful to humans, including the bacterium that causes Lyme disease. As tick-borne diseases become increasingly common in the U.S., scientists are scrutinizing these external parasites’ relationship with their hosts with the goal of figuring out how to fight the spread of Lyme. Ticks aren’t born with the pathogens that cause the main tick-borne diseases in humans; they get them from feeding on animals that act as reservoirs of the bacteria and parasites. Scientists are especially interested in the host that seems to be by far the best at harboring Lyme disease: the white-footed mouse. And some researchers have noted that an abundance of the mice one year is linked to more Lyme disease in humans the next — suggesting that this relationship could matter a lot when it comes to reducing Lyme disease.

Tick-borne Lyme disease is now the most common disease transmitted to humans via blood-sucking pests in the U.S., and the problem is expected to get worse. The Centers for Disease Control and Prevention estimates the number of cases at about 300,000 per year. Lyme disease, which causes fever, fatigue and headaches, can usually be successfully treated with antibiotics; when untreated, it can become a chronic, debilitating condition. Previously unknown tick-borne pathogens — at least a dozen since 1967 — are being discovered as well. And “there’s no reason to think we would have found everything,” said Ulrike Munderloh, a professor of entomology at the University of Minnesota.

The white-footed mouse is not only the most efficient known reservoir of Borrelia burgdorferi, the bacterium that causes Lyme disease, but the rodent is expanding its range, which currently covers 41 states. The narrowing footprint of forests, fragmented by roads and developments and sliced into backyards, often leaves the white-footed mouse as king of the forest, able to scamper about and reproduce without fear of predators, perhaps contributing to increased rates of tick-borne diseases in humans.

Scientists who study ticks and Lyme disease are keeping a close eye on how what happens in the forest affects the spread of the disease. A few years ago, scientist Rick Ostfeld of the Cary Institute of Ecosystem Studies in Dutchess County, New York, noticed a key pattern tied to a favorite mouse meal: lots of acorns = lots of mice = lots of Lyme disease in people. So when he and Bard College biology professor Felicia Keesing noted a bumper crop of that favorite mouse snack in the areas where they work in eastern New York in the summer of 2015, they weren’t surprised by an influx of mice in 2016. And now they’re bracing for more cases of Lyme and other tick-borne diseases there and possibly in nearby southern New England and the mid-Atlantic.

The possibility of breaking that chain of events led Keesing and Ostfeld to embark on a five-year experiment they call The Tick Project. Keesing and Ostfeld recruited almost 1,000 households in eastern New York that are at high risk for Lyme disease — they think of them as red zones, Keesing said, where people are reluctant to buy homes for fear of the disease — for the project and set up each yard with a bait box and fungal insecticide spray. The bait boxes, which attract mostly mice but also other small rodents such as chipmunks and shrews, deliver a dose of a pesticide that kills ticks that try to feed on the animals for the next couple of months. Vegetation in the yards is doused with a fungal spray that also kills ticks. While Keesing and Ostfeld are just beginning to collect data, they say that if people encounter fewer ticks or there are fewer cases of Lyme disease in the area they’re studying, the methods could be implemented elsewhere after the study concludes in 2020.

“We could spend our whole careers researching what not to do, but what do you tell your friends and neighbors in high-risk areas?” Keesing said. “They may have been interested [in our other research], but it didn’t really help them in any profound way.”

Kevin Esvelt, an evolutionary engineer at MIT, is also targeting the white-footed mouse, although his idea to tackle the tick-borne diseases is taking a more radical route: editing the mice’s DNA to make them unable to pass bacteria and viruses to ticks.

“When engineering a complex system, you should always make the smallest possible change that could solve the problem,” Esvelt said. “For tick-borne disease, that means preventing the ticks from being infected by white-footed mice. If we’re looking exclusively at Lyme disease, the contrast is clear: immunize every at-risk human indefinitely or heritably immunize the mouse population once? The latter is arguably more parsimonious, but reasonable people may prefer one or the other depending on their values.”

His early-stage efforts — his lab is still identifying the genes that would be edited — have been part of ongoing ethical debates about manipulating wild animals in communities where he would conduct the experiment. But Esvelt said he would proceed only with residents’ blessing. At first, that would be limited to islands, where the mice would be able to spread the new genetic code. That’s at least seven years out, and introducing the genetically engineered mice to the mainland would require a massive effort and tack on several years. But choosing the mouse was a no-brainer. “By immunizing the mice against tick saliva, we may be able to block babesiosis, anaplasmosis, ehrlichiosis and Powassan virus, as well as the Borrelia that cause Lyme disease,” he said.

Ecosystems are complicated. And when it comes to Lyme disease, the risk to humans is affected by more than ticks and mice: Deer provide a place for ticks to mate, for example, so an ample deer population has been linked to the disease. Keesing’s team found that opossums, on the other hand, tend to eat or groom off most of the ticks they come into contact with, so more opossums in an ecosystem could mean a reduction of the disease in humans. But the role of the white-footed mouse is so important in spreading tick-borne diseases that Dr. Bobbi Pritt always works it into the discussion. “Interventions to decrease the mice [population] could potentially prevent Lyme disease” and other tick-borne diseases too, said Pritt, whose team discovered a new bacterial species that causes Lyme disease while leading research on parasites and vector-borne diseases at Mayo Clinic in Rochester, Minnesota.

The expanded range of the white-footed mouse can also clue scientists in to where tick-borne diseases may spread.

“Both in the upper Midwest and in southeastern Canada, there is clear evidence that the white-footed mouse is expanding its geographic range quite rapidly to the north, with evidence that climate change is one of the important causes,” Ostfeld said. “This is a concern because it will expand the area over which the black-legged tick will have access to the most competent reservoir for Lyme and other tick-borne diseases. In fact, we should expect the expanding populations of mice to bring along with them populations of black-legged ticks.”

Differences in climate and ecosystems between the Northeast and Midwest mean the disease may spread in slightly different ways in the two locations. Other animals may play a bigger role in tick-borne diseases in the Midwest, some researchers have suggested. Slightly larger animals such as chipmunks live longer; it’s possible that they carry more loads of ticks over their lifespans than mice do, Munderloh said. Still, black-legged ticks and white-footed mice seem to be extending their range in tandem: Both were rare finds north of U.S. Highway 2, which slices across Minnesota from the Red River to Lake Superior and used to act as a rough dividing line between the stomping grounds of the white-footed mouse and its nearly indistinguishable cousin, the deer mouse, said David Neitzel, supervisor of the Vectorborne Diseases Unit at the Minnesota Department of Health. Now, the white-footed mouse is found in most counties in Minnesota, said Gerda Nordquist, animal survey supervisor at the Minnesota Department of Natural Resources. And the black-legged tick was established in 45 of the state’s 87 counties in 2015, up from just nine in the 1990s.

Although it’s tempting to blame one factor for the increase in Lyme disease — in addition to the white-footed mouse, climate change and the black-legged tick are often mentioned as single culprits — researchers say it’s important to consider the entire complex system.

“I don’t know if there’s ever going to be one silver bullet,” Neitzel said. “There will have to be a variety of control methods — public education, personal protection, control of ticks on the host, control of ticks in the environment, vaccines. All of these put together will likely be what’s most effective.”

CORRECTION (July 6, 7:45 p.m.): An earlier version of this article incorrectly categorized ticks as insects. They are arachnids.