Who would have thought that a squid would go to space before you? Yes, you read right, a squid… For those of you who think that science might be boring, here I bring you the latest and tastiest research where Ana has participated: the Understanding of Microgravity on Animal-Microbe Interactions (UMAMI) experiment. They decided, because why not, that it would be a great idea to send a squid to space to investigate the effect that microgravity has on the interactions between a host and its biological guests. But let’s trace back a bit and start from the beginning.
Nowadays, it is widely known that we coexist with, and even depend on, plenty of microbes to survive and live healthy lives. The microbiome has become one of the hot topics of science in recent years. Even so, scientists decided to take it one step further and brought it to space. The idea behind the study was to analyze how microgravity impacts the colonization of hosts by their beneficial bacteria, and the impact that it has on the molecular and biological stress that these extreme conditions imply for living beings.
However, you might be asking, why a squid in the first place? Well, the organism selected for the mission was the perfect candidate. The Hawaiian bobtail squid (Euprymna scolopes) is a tiny 3 mm animal that can be easily stored and transported. It establishes a symbiotic relationship with the bacteria Vibrio fischeri. V. fischeri colonizes the belly of the squid, where it produces the characteristic bioluminescence of this animal. However, the bacteria are vital for much more than just a cool glow. As is becoming more known, bacteria also aid their hosts in regulating stress and immunology.
The squid offers its light organ to Vibrio fischeri as a cozy home, but getting them there in space requires some clever engineering. To pull this off, the UMAMI experiment used automated fluid processing cassettes aboard a SpaceX flight. The squids were divided into two main groups: a symbiotic group (SYM) that received the V. fischeri bacteria once they reached microgravity, and an aposymbiotic control group (APO) that only received sterile seawater. At specific time points, 0, 2, 6, and 12 hours, the experiment was automatically stopped, and the squids were preserved in a fixative so scientists could take an exact snapshot of their gene expression.
In order to validate the colonization by V. fischeri, a double control was performed. First, the presence of the bacteria was directly confirmed post-flight using specific digital PCR sequencing. Then, its correct integration with the host was validated through the transcriptomic shift in the squid’s body. There are different genes that are naturally upregulated in the squid when this biological handshake happens, such as peptidoglycan receptor proteins (PGRPs), galaxins, and lipopolysaccharide binding proteins (LBPs). In the case of the SYM group, these genes showed increased expression compared to the APO group, proving the connection was made.
Once it was clear that the colonization had taken place correctly, the researchers began to look at the stress response. Environmental stress produces reactive oxygen species (ROS), which the cells have to counteract by producing ROS-degrading enzymes and lipid transport proteins to mitigate the damage done to the cell membranes. These kinds of proteins, and their respective genes, were observed to be highly increased in the bacteria-free APO squids. On the other hand, just 2 hours after colonization by V. fischeri, there was a massive decrease in these stress genes in the SYM squids. The bacteria are there not only to light the way, but also to decrease the stress and reduce the production of harmful ROS. More than a molecular handshake, V. fischeri gives a molecular embrace.
The changes that spaceflight induced could be seen in other aspects of the squid’s biology, too. Lipid profiles were significantly altered, with an increased production of ceramides. Ceramides are powerful lipid modulators that act as indicators of stress, triggering cell differentiation and even apoptosis (cell death). The metabolic profiles were also highly modified by microgravity. While the overall levels of the amino acid tryptophan remained about the same, the stressed-out APO squids drastically increased their breakdown of it via the kynurenine pathway, a classic sign of tissues trying to scavenge reactive oxygen species and deal with inflammation
However, not all hope was lost. The SYM squids—those that were inoculated with Vibrio fischeri—had much less severe stress responses than the APO group. As mentioned before, the molecular embrace of V. fischeri acted as a “calming” mechanism for the squid’s innate immune and stress responses. After colonization, the SYM squids presented reduced oxidative stress. Furthermore, instead of leaning on the kynurenine pathway, the SYM squids showed a decrease in those metabolites and an increase in other immunosuppressive molecules like urocanate and xanthine, indicating lower tissue inflammation. This aided the host in maintaining better homeostasis during spaceflight.
Finally, one of the most shocking findings was that, far from the colonization and tissue development being slowed down by the harsh environment of space, the squids colonized by V. fischeri actually experienced accelerated bacteria-induced development. Surprisingly, isn’t it? Scientists expected that the colonization could be poor, since the mechanisms the squid uses to help V. fischeri reach the light organ can be negatively altered in space conditions, such as the shortening of cilia. However, the colonization was carried out perfectly, and development kicked into high gear. This was first observed as an increase in neurogenesis in the SYM squids in space, indicated by upregulated neuronal differentiation genes just 2 hours after inoculation (compared to 6 hours for the squids on Earth). The lipid signaling and presence of ceramides was also higher and peaked earlier in these squids. These lipids quickly triggered the cellular remodeling of the light organ’s tissue so the symbiosis could be fully established.
So… what did we learn from this crazy experiment? Well, firstly, that there is still much to learn from our relationships with the organisms that live on Earth, and the impact that space might have on us and them. Then, some other cool science facts. One of the most relevant is that it was proven that host colonization can be successfully performed during the microgravity of space. Beyond that, it shows that the relationships between host and microbe are fundamental to aiding the host in regulating the stress that these radical conditions impose on our bodies.
Isn’t it crazy when you think about it? Even though it was not designed to ever experience microgravity, an organism identifies it as a stressor and acts accordingly. Even so, what is more outstanding to me is the fact that the bacteria that interact with us might be the key to reducing that stress and aiding us during space missions. Who would have said that the solution was truly inside of us…
There is still much to unravel and discover from these relationships, but as was once said… A small step for squids, a giant leap for science… or something like that.