The lungfish is a rarely studied organism, with scientific implications that extend far beyond its unassuming reputation. On Thursday, Oct. 23 the Biology Department Seminar Series featured Irene Salinas, an evolutionary immunobiologist at the University of New Mexico-Albuquerque who presented her extensive research into the immunobiology of the African lungfish.
The lungfish is usually phylogenetically placed as a transitional species — one showing intermediate traits at a specific stage of evolution — in the animal move to land. This species is placed at this divergence point because lungfish are amphibian-like, able to survive both in water and on land. This aspect is key to their adaptability, as the specific African lungfish studied by Salinas are often exposed to extreme drought conditions, requiring them to move from water to land seasonally in a process known as estivation. These lungfish are unique, even when compared to their counterparts like Australian lungfish, because they form cocoons: mucosal structures that they can form outside their bodies that enable them to survive harsh droughts for several years at a time and emerge alive.
Salinas explained that these cocoons are much more interesting on the cellular level than they may initially appear. For one, the mucosal tissues needed for the cocoon are able to undergo massive tissue destruction and regeneration cyclically with the changing of the seasons. Key cells required for mucus secretion like goblet cells can be regenerated by stem cells, then destroyed during inflammation. Every year, the African lungfish is able to transition between aquatic and terrestrial states. Furthermore, these organisms have the largest number and most diverse granulocytes (the most common cell in the innate immune system) of all animals.
When Salinas investigated the cocoon layers, she observed the hypothesized redistribution of granulocytes to the mucosal cocoon. This ensured bacterial organisms would be trapped and destroyed outside the lungfish rather than successfully infecting it. The layers of the cocoons even showed differences in their regeneration at different points in time, further indicating that the lungfish could alter specific parts of its cocoons in response to external cues. A key process of NETosis in the granulocytes was found, where the lungfish formed extracellular casts of DNA with antimicrobial proteins that could trap pathogens.
These data were ripe for scientific discovery, as Salinas soon found.
“There's a lot of hidden information in the dark matter of big data sets. But luckily, one day, I was giving this talk… and stared at [my] screen while [I was] giving [the] talk… and all of a sudden I noticed something weird,” she said.
The interesting observation Salinas made were segments in the lungfish genome that produced a toxin of unique phylogenetic importance, with no typical analogue in vertebrates. In fact, this toxin was also expressed in the Australian Lungfish — although genetic analysis showed that the African Lungfish had a genetic sequence for a far more complex modification and production of the toxin. Through studying the specific structure of the protein, Salinas provided insights into further mysteries, like how the toxin avoided causing toxicity to humans but remained a powerful antimicrobial agent, and potentially even an insecticide. These biochemical data could explain the fish’s survival and defense against pathogens while in its terrestrial cocoon.
Salinas addressed the various hypotheses her lab tested regarding the toxin’s origin and use, both in the stable and mucosal states of the lungfish. These suggestions included the toxin’s implication in inflammation, its use in “chemical warfare” against bacteria or fungi and even its potential role in the activation of stem cells. Special emphasis was placed on its possible use to ward off insects, which is especially important considering that lungfish exist in environments where insect-based diseases like dengue are significant concerns. Working closely with experts in the field, the lab was able to obtain experimental findings supporting this idea, which even led to a patent.
Concluding her seminar with a round of questions, Salinas highlighted the biological significance and regenerative applications of studying African lungfish further.
“[Most of their internal organs] suffer incredibly during an estivation, because they're not eating for seven years. The gut changes a lot…we return them to water, and within three days, these tissues are built again. And that's incredible from a general biology perspective.”
