Mohamed Salem and his team spend their days looking for invisible signs of stress in subjects who can’t tell them something is wrong. They can’t talk, because they’re fish, but the researchers are keen to understand their inner lives, because stressed-out fish don’t grow well and are more susceptible to disease.
But it’s about more than just good animal husbandry for Salem. Globally, more than 3.3 billion people get at least 20% of their daily animal protein from fish, and with rising water temperatures threatening commercial fish stocks and increasing demands on modern fish farming, understanding and preventing fish stress is critical for both conservation and the world’s food supply.
That’s why Salem, a professor of animal and avian sciences, and his team of student researchers set out to find a more practical way to measure the effects of fish stressors like heat, low oxygen, overcrowding and improper diet. It turns out the fish have been talking all along through the language of genetics.
“We are essentially developing a translator for the fish’s biological experience,” Salem said, “By decoding these genetic signals, we can hear what the fish are telling us about their environment long before they show outward signs of distress, allowing us to intervene and ensure their well-being.”
Traditionally, scientists test levels of the hormone cortisol in fish blood to determine stress. But that’s an unreliable measure, so the team has been looking for something more precise.
Every cell in an animal’s body is constantly reacting to the world around it on a genomic level, and those reactions leave behind a trail of evidence. For example, when we go out into the sun, our skin cells turn on genes involved in DNA repair and turn off genes involved in cell division to prevent damage from being copied. Reading which genes have been turned on and off can reveal a great deal about an animal’s environment.
The challenge for Salem was the sheer number of genes in a fish and the possible responses they could have to different stressors. When he and the students in his lab exposed rainbow trout to five different kinds of stress, they found that more than 21,000 genes were either switched on or switched off, and each type of stress created its own unique genetic signature.
Of course, monitoring all those genes to identify stress is impractical, and Salem wanted to find just the key changes. It’s sort of like analyzing changes in a city during a snowstorm, like traffic jams, school closures, people in coats, to find that cold temperatures and white fluff on the ground are the two most reliable indicators.
To sift through all their data and identify patterns in fish genes, Salem’s team turned to machine learning with the help of high school intern, Youssef Ali, who is now a rising sophomore at the University of Maryland College Park.
Under the guidance of Ph.D. student Guglielmo Raymo, Ali first looked for a handful of genes that could identify any kind of stress. The AI algorithm identified 39 core genes associated with stress, but it was unable to accurately predict stress in fish it hadn’t seen before.
So, the team took another approach and focused on just one type of stress: heat. After searching through more than 12,000 heat-related genes, the algorithm narrowed the possibilities from thousands to hundreds to dozens, until just two remained. Together, they were a nearly perfect biomarker, predicting heat stress in rainbow trout with up to 98.6% accuracy.
“It could be a game changer,” Salem said, “a simple, elegant and incredibly powerful tool that gives us a real-world, practical framework for actually improving stress resilience in fish.”
The discovery, published in the journal Nature Scientific Reports, provides fish farmers and conservationists with a tool to identify when fish are in danger. So far, the work has focused on rainbow trout, but the genetic markers identified by Salem and his team are present across fish species.
“If they prove transferable, it can help conservationists monitor wild fish populations, and fish farmers monitor health and environmental stress in aquaculture systems,” Salem said. “And it can even be used in breeding programs to select for fish that are naturally more resilient to heat.”
The team is now expanding its work to identify similar markers for other kinds of stress, developing the tools to hear what the fish genes are telling them across a broad range of environmental conditions.
-Kimbra Cutlip
First Year Student is the Driving Force Behind Prestigious Scientific Paper
Not many first-year college students co-author research papers in highly cited journals. But Professor Mohamed Salem says Youseff Ali was the driving force behind his recent paper. It’s an accomplishment that was seeded at the end of Ali's sopho-more year of high school. “I was taking biology, and I got interested in doing research,” Ali recalls. “I emailed a number of professors to see if there was an opportunity, and Dr. Salem answered.”
Salem’s aquaculture lab in the AGNR Department of Animal and Avian Sciences offered Ali the chance to work on two important issues; adaptation to climate change and feeding the world sustainably. The lab focuses on genomic methods to improve the health and growth of commercially important fish, which are heavily impacted by changes in water quality and temperature.
What Ali offered Salem and his team was an enthusiastic and knowledgeable approach to a large volume of data they had been collecting.
Salem’s PhD student Guglielmo Raymo took Ali under his wing as an intern, and they began asking scientific questions that weren’t possible before—among them, can we find a simple signal in a fish’s DNA to tell us when it’s stressed?
Three years later the researchers had an answer. Yes, they could—at least for heat stress. And it was published in the journal Nature Scientific Reports at the end of Ali’s first semester at AGNR.
“It’s very encouraging to be a real part of this research, contributing to something meaningful toward the greater good,” Ali said. “And working with such a fantastic team, with such expertise was great motivation.”