South SFV Today

Many organisms, including humans, are comprised of a variety of microbes. However, some creatures have even more unique connections. Acoels, distinctive marine worms that can regenerate their bodies after injury, form symbiotic relationships with photosynthetic algae living inside them. These collections of symbiotic organisms are known as a holobiont. The manner in which these organisms communicate is a subject that scientists are striving to understand, particularly when the species involved are an animal and a solar-powered microbe.

Bo Wang, assistant professor of bioengineering at Stanford's Schools of Engineering and Medicine, has begun to find some answers. His lab collaborates with the University of San Francisco to study Convolutriloba longifissura, an acoel species that hosts the symbiotic algae Tetraselmis. According to recent research published in Nature Communications, the researchers discovered that when C. longifissura regenerates, a genetic factor involved in the acoel regeneration also controls how the internal algae react.

"We don't know yet how these species talk to each other or what the messengers are. But this shows their gene networks are connected," said Wang, who is a senior author of the paper.

Holobiont is a relatively new concept and scientists still aren't sure about the nature of some relationships. The term "acoel" is Greek for "no cavity," as these worms have no separation between their inner and outer organs (called a coelom). In these animals, all organs share the same space. Some acoels also host symbiotic algae within their organ space where they perform photosynthesis. This relationship provides safety for the algae and extra energy from photosynthesis to the acoel.

"There was no guarantee that there was communication because the algae are not within the acoel’s cells; they’re floating around them," says James Sikes, researcher at the University of San Francisco and co-senior author of the paper. Sikes has been studying acoels for about 20 years, noting that their symbiotic relationship sets them apart from other regenerating animals like planarian flatworms and axolotls.

When these acoels reproduce asexually, they first bisect themselves. The head region grows a tail and becomes a new acoel. The tail, however, grows two new heads which then split into two separate animals. Animal regeneration requires communication across many different cell types, but in this case, it may also involve another organism entirely. Researchers were curious about how the algal colonies inside reacted to this process – particularly whether they continued to photosynthesize as normal and if not, what was controlling that? This was especially puzzling as the team found that photosynthesis wasn’t required for acoels to regenerate – they could do it in the dark. However, there must be conversation between the species for their long-term survival.

"Testing if photosynthesis was affected was an adventure. None of us knew what we were doing," says Dania Nanes Sarfati, lead author of the paper and former doctoral student in Wang’s lab at Stanford Bio-X Bowes Fellow. "One of the most exciting things was that we could actually measure algal photosynthesis happening inside the animal."

Through sequencing, the team differentiated the genes of the two species and determined which pathways responded to injury. These measurements helped them realize that during regeneration, the algae inside underwent a major reconstruction of their photosynthetic machinery – but how it was being controlled came as a surprise.

During regeneration, both the acoel’s regrowth and algal photosynthesis appeared to be controlled by a common transcription factor in acoels called runt. After injury, runt is activated initiating the regeneration process while algal photosynthesis drops off. There is an upregulation in algal genes associated with photosynthesis – likely to compensate for the loss in photosynthesis due to the split. However, when researchers knocked down runt, it halted both regeneration and the algal responses.

Runt is highly conserved, meaning the same factor is responsible for regeneration in many different organisms, including non-symbiotic acoels. But now it’s clear that instead of just controlling the acoel’s regenerative process, it also controls communication with another species.

Understanding how partners in symbiotic relationships communicate at the molecular level opens up many new questions for this field of research. "Are there rules of symbiosis? Do they exist?" said Nanes Sarfati. "This research sparks these kinds of questions, which we can link to other organisms."

Wang believes this introduces more ways of investigating how symbiotic species interact and couple with each other to form holobionts. Some interactions could be potentially driven by chemicals, proteins, or environmental factors. However, these interactions are now becoming vulnerable points under climate change's challenge, causing symbiotic partners to separate. Sikes highlighted that he, Wang, and Nanes Sarfati all began from the animal side of the symbiotic relationship but realized that algae respond to host injury as well, potentially sparking similar questions in other systems.

"We often assume we know a lot, but we’re humbled when we look at different species," Wang said. "They can do things in completely unexpected ways, which highlights the need to study more organisms and is becoming possible with technology."

Additional Stanford co-authors include former graduate student Yuan Xue; PhD student Eun Sun Song; Stephen Quake; and Adrien Burlacot. This research was funded by a Bio-X Bowes Fellowship, a Stanford Interdisciplinary Graduate Fellowship, the Beckman Young Investigator Program, the Carnegie Institution for Science, and the National Institutes of Health.