Terps Take on Ticks

A pair of studies out this month from University of Maryland researchers puts the crosshairs on a parasite endemic to our region that’s responsible for transmitting Lyme disease and other serious infections to hundreds of thousands of Americans yearly.

One provides an unprecedented overall look at the genome of the black-legged tick, or deer tick, while the other uncovers a specific process key to interactions between ticks and their hosts; together, they open the door to new vaccines and other approaches to mitigating the harm of potentially debilitating tick-borne diseases.

"This tick is present everywhere, and it transmits diseases all over the globe, but it doesn’t transmit a disease everywhere in the same numbers,” said Utpal Pal, senior author of both studies and a professor in the Virginia-Maryland College of Veterinary Medicine at College Park who has been pursuing black-legged tick investigations for decades. “To understand why, we need to understand the genetic differences and the molecular mechanisms underlying tick biology. Our work makes huge advances in these areas."

In a study published last week in the journal Nature Genetics, a UMD team presented the first comprehensive, continuous genome for the black-legged tick, identifying thousands of novel genes and new protein functions, including proteins associated with tick immunity, disease transmission and developmental stages.

The publication—including first co-authors Sandip De and Chrysoula Kitsou, assistant research professors in the veterinary medicine program—far surpasses previous efforts to sequence the tick’s genome, which resulted in partial genomes or fragments of genome with gaps and uncertainties.

“There are so many unanswered questions about how these parasites evolved and transmit disease,” Pal said. “We believe there are genetic factors that contribute to why these ticks are so good as disease vectors, but we can’t really understand it without a very good genome like this.”

Now, scientists can begin to unravel the molecular mechanisms behind many aspects of the parasite’s biology and its interactions with both hosts and the diseases it transmits.

In another study published Jan. 13 in the journal Science, Pal and colleagues identified the first inter-species signaling pathway between an arthropod parasite and host, where molecules in the blood of a host animal trigger the immunity and development of a parasite.

The study showed that when ticks feed on the blood of mice infected with the bacteria Borrelia burgdorferi, which causes Lyme disease, a protein from the mouse immune system binds to receptors on tick cell surfaces and signals the tick's organs to develop more rapidly, producing an immune response long before the bacteria itself can begin to infect the tick.

The research, which included first author Vipin S. Rana, assistant research scientist in the veterinary medicine program, identifies a potential target for anti-tick vaccines or therapeutics to prevent the spread of infections like Lyme disease. The findings also provide important new insights into the evolution of biomolecular interdependencies between species, and highlight, for the first time, both the integration of immunity and animal development and the adaptability of an ancient cell signaling system or pathway that all plant and animal cells use for sensing and responding to their environment.

“Understanding that this pathway integrates immunity and development has important implications for potential strategies to prevent tick-borne disease transmission,” Pal said. “Because if you delete the pathway, ticks with malformed mouthparts cannot feed or transmit disease. But what is also really exciting to me is that we see this sort of early-warning system, where the tick’s immune system indirectly detects a pathogen using an immune response from its host rather than the pathogen itself, accelerating its own development.”