It’s been a mystery hiding in plain sight.
Researchers working with tiny worms called Caenorhabditis elegans—a common lab organism used to study basic principles of biology—know not to raise the temperature above about 80 degrees Fahrenheit because the worms start to die.
Yet some populations of C. elegans in the wild thrive above that temperature, such as those that live in Athens, Georgia, and Ceres, South Africa.
The worms belong to the same species, so why do they have such different tolerances to heat?
The heads of three genetics labs at Harvard Medical School have teamed up to find out—and not solely because they’re interested in worm biology.
The answer, they believe, could inform efforts to protect species from the ravages of global warming.
Feeling hot, hot, hot
As the Earth’s temperature creeps higher, increasingly volatile weather patterns leave regions vulnerable to record-breaking heat and cold. The world has recorded nearly twice as many extremely hot days each year in the last few years as it did annually in the preceding half-century, according to the National Oceanic and Atmospheric Administration.
While some organisms can withstand the new trends and extremes, many others struggle and die. Observing that warmer climes can harm aspects of physiology from metabolism to reproduction to embryonic development, scientists have revealed some, but not yet all, of the reasons behind such temperature sensitivity.
Part of the problem arises at the cellular level: Certain essential biological structures and processes break down when it gets too hot or cold.
“When you move a cell ten to 15 degrees outside its normal temperature range, everything falls apart,” said Max Heiman, associate professor of genetics in the Blavatnik Institute at HMS and associate professor of pediatrics at Boston Children’s Hospital. “Why?”
It’s not a question Heiman, who studies the nervous system using C. elegans as a model, normally thinks about. But when the HMS Department of Genetics sent out a special call for research proposals related to climate change in late 2019, he considered his work from a new angle.
C. elegans, he realized, could help answer questions about “why biology doesn’t work at all temperatures.”
Heiman recruited fellow C. elegans specialists Keith Blackwell, professor of genetics at HMS and associate research director at Joslin Diabetes Center, and Monica Colaiácovo, professor of genetics in the Blavatnik Institute at HMS. Together they wrote a proposal.
The team was named a competition finalist, earning $100,000 in research funds.
System failure
The three geneticists are now applying their scientific strengths to seek new insights into what hot environments do to biological systems.
First, they’ve brought in strains of C. elegans from sites with a range of climates around the world, including Chile, Italy, Japan, South Africa, and the southern U.S., to compare with the standard lab strain, which derives from compost heaps near Bristol, England.
When pandemic restrictions allow, the researchers will split each strain into groups, cultivate each group at a different temperature, and observe how each temperature does or doesn’t affect a particular facet of worm biology.
In this case, the disease is climate change, and we have a faith that understanding the basic processes affected by it will inform our attempts to adapt to it.
Max Heiman
HMS associate professor of genetics
Each team member will focus on their favorite thing to study, said Heiman. He himself is looking at neural development; Blackwell at the cellular response to oxidative stress, an imbalance between free radicals and antioxidants; and Colaiácovo at meiosis, the type of cell division that produces sperm and eggs.
Testes in mammals keep sperm cooler than the rest of the body for healthy meiosis, Heiman points out, and researchers have known for decades that a subtle increase in temperature disrupts meiosis and produces more male offspring in C. elegans, yet few have explored why that may be, said Colaiácovo.
“It will be great to work with Max and Keith so we can look at the effects of heat from lots of different vantage points,” she said.
Then, the team will compare its observations to the different strains’ genetic sequences in an effort to link temperature tolerance—or intolerance—to specific DNA variants. Blackwell is also looking beyond the DNA itself to the dynamics of how certain genes are activated or deactivated.
“It will be very interesting if the worms’ stress defenses can be ‘reset’ so they adapt to different climate niches,” Blackwell said.
Wider than worms
If they’re able to provide genetic explanations for how C. elegans can withstand high temperatures, the researchers can then explore whether manipulating individual genes or combinations of genes could help less heat-tolerant worms—or even other organisms that share those genes—stay vibrant as temperatures rise. Safely introducing such modifications into real-world environments could strengthen food chains where C. elegans forms the bottom rung, Colaiácovo speculates.
The researchers also hope their findings will apply beyond worms, such as by informing predictions about which species have the genetic capacity to adapt to rising temperatures and which will falter. That could improve models of the effects of climate change, said Heiman.
The group continues to ponder potential applications.
Although climate change at first seemed far afield from their everyday work, the researchers have found deep connections.
“Everything we do as basic scientists comes from the point of view that understanding a process will help us deal with it, such as figuring out how to treat a disease,” said Heiman. “In this case, the disease is climate change, and we have a faith that understanding the basic processes affected by it will inform our attempts to adapt to it.”
