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A new study that started as a student project from the MBL Ecosystems Center and Brown University reveals genetic and other biological mechanisms that allow a parasitic worm to manipulate its host.

Salt marshes are home to tiny crustaceans called amphipods that keep a low profile: Their gray-brown coloring helps them blend in with their surroundings, and they spend most of their time hiding under vegetation. But when amphipods are infected with a parasitic worm called a trematode, they turn bright orange and lose their tendency to run for cover when exposed. This bizarre behavior makes them stand out to predators — as well to scientists.

Over time, with advancements in molecular genetics, computational tools and biomedical technology, faculty and student scientists have made unexpected discoveries about the relationship between amphipods and the parasitic worms that prey upon them.

In published in Molecular Ecology, researchers provide a detailed analysis of the molecular mechanisms that allow the parasites to manipulate their hosts, and explain what’s happening to the amphipod’s biology that causes it to respond to the parasite in such distinct ways.

The work started in 2013 as part of the Brown University-Marine Biological Laboratory research program that trained students “to think interdisciplinarily and to apply genomic techniques to ecological and evolutionary questions,” said Zoe Cardon, senior scientist at the MBL Ecosystems Center. 

“Characterizing the molecular mechanisms of manipulation is important to advancing understanding of host–parasite coevolution,” said study author David Rand, a professor of natural history and chair of the ecology, evolution and organismal biology department at Brown.

The relevance of the findings extends far beyond the salt marsh, Rand said, especially when considered in context of certain pathogens that infect humans.

The evolution of a biological research project

The trematode worm’s interaction with the amphipods makes Darwinian sense, according to Rand. Parasites manipulate hosts to ensure their transmission so they can continue to reproduce. They’re an example of “prudent parasites” that don’t kill their hosts right away or ever, giving the parasites time to reproduce or move to another host.

The type of “zombie” manipulation seen in the amphipods isn’t unheard of in the natural world. However, Rand said, less has been known about the precise ways that parasitic worms have been able to cause changes in the amphipods that affect behavior, appearance and immune function.

Anne Giblin, Director of the MBL Ecosystems Center, credited David Johnson of the Virginia Institute of Marine Sciences for recognizing the implications of the orange amphipods. “Other people had not even noticed them, or if they had, simply thought it was a different species.   David knew this was an unusual color morph of a common species and figured out the color was a result of an infection by parasites,” said Giblin. 

In the new study, the scientists used RNA sequencing to identify genes whose function match the three big changes in the host’s traits. They discovered that trematode infection results in activation of amphipod gene transcripts associated with pigmentation and detection of external stimuli, and suppression of multiple amphipod gene transcripts implicated in immune responses.

The researchers hypothesized that suppression of immune genes and the altered expression of genes associated with coloration and behavior may allow the parasite to persist in the amphipod and engage in further biochemical manipulation that promotes transmission.

In the paper, researchers concluded that the genomic tools and transcriptomic analyses they reported provide new opportunities to discover how parasites are able to alter the diverse molecular pathways that underlie or determine changes in their hosts.

The research began in 2013 as a collaborative project intended to engage graduate students in sequencing DNA and RNA for questions in the realm of ecology, evolution and environmental science. Every year, a group of Brown Ph.D. students studying subjects including biology, applied math and computer science would take a field trip to a research site at Plum Island Ecosystems Long-Term Ecological Research site (PIE LTER), which is run by the MBL Ecosystems Center. 

Cardon said she loved the interdisciplinary nature of the work and said that kind of thinking is important in any type of research. 

“Learning to think broadly and work across disciplinary lines is the future of research,” said Cardon, “Many students have wonderful training in very specialized areas, and that is definitely valuable. But we need to be able to collaborate across disciplines, especially when we're facing the monumental planetary change developing all around us today.”

The project was supported by a National Science Foundation IGERT award in Reverse Ecology (NSF DGE 0966060); NSF support for the Plum Island Ecosystems Long-Term Ecological Research site (NSF OCE 1637630); and other awards from the National Institutes of Health (R01GM067862, 1R35GM139607, P20GM109035, NSF DEB 1902712).

Citation:

Rand, D. M., Nunez, J. C. B., Williams, S., Rong, S., Burley, J. T., Neil, K. B., Spierer, A. N., McKerrow, W., Johnson, D. S., Raynes, Y., Fayton, T. J., Skvir, N., Ferranti, D. A., Zeff, M. G., Lyons, A., Okami, N., Morgan, D. M., Kinney, K., Brown, B. R. P., Giblin, A. E., & Cardon, Z. G. (2023). Parasite manipulation of host phenotypes inferred from transcriptional analyses in a trematode-amphipod system. Molecular Ecology. DOI:

This story heavily excerpted a press release from Brown University News. Source: