Jamie Foster: squids in space
"Click here to listen to the full podcast episode"
Dr Sally Le Page chatted with Professor Jamie Foster, a microbiologist at the University of Florida working on symbiotic relationships between host animals and their microbes. Part of her research involves sending baby squid into space. That’s right, glowing squid in space. So first things first, who are the partners in this symbiotic relationship, and why does a squid need to glow in the dark?
Jamie: This symbiosis is unique in a few different ways. First of all, it's a partnership between a bioluminescent bacteria - bacteria that has the ability to glow in the dark, essentially - and the bobtail squid. The Latin name, the scientific name, is Euprymna scolopes, and this is a squid that's indigenous to Hawaii and not a lot of people know about it. Even when I started working on this animal 30 years ago, even a lot of local folks from Hawaii didn't know about the little squid that glowed in the dark around them.
Jamie: They're only about maybe three or four centimeters in length. So they're very small and that's full grown. And when they're born, they're only about two or three millimetres. We call them paralarvae because they're just like miniature adults when they're born. And they're incredibly cute. So once you've seen one, you're going to fall for this little creature, because they're very adorable.
Jamie: And then the other partner in all of this is a bacterium called Vibrio fischeri. And there's a lot of bad Vibrios out there, things that can make you sick if you eat shellfish that's not cooked properly. But this Vibrio is a very benign, friendly sort that doesn't cause disease in its hosts. And it colonises a very special organ called the light organ of the squid.
Jamie: And this symbiosis has evolved for over millions of years to give the squid the ability to use that light made by the bacteria to hide from predators. And we call that whole process counter-illumination. It's kind of like a Harry Potter cloaking device. The squid is able to use the light from the bacteria and hide itself from the downwelling moonlight. So it's basically casting no shadows so any predator looking up can't see the squid.
Sally: This is surprising to me, is that shining light makes you more hidden.
Jamie: Right!
Sally: I would have thought that shining a torch in the middle of the ocean. You're lit up. You're making yourself more obvious.
Jamie: Well, in a way, if you imagine if you're standing in front of the headlights of a car and then you shine your flashlight out, you're matching the light coming from behind you. Thus, you're hiding your shadow that would be apparent in the light. So it's just a way for you to manipulate your environment and camouflage yourself.
Jamie: And so this is a little different in the symbiosis world, because most of the time in the symbiosis world you're exchanging nutrients. And there is an exchange of molecules and food, but instead of bacteria feeding the animal, it's the animal feeding the bacteria. And that's a little unusual because they're getting this behaviour out of this relationship. The squid can live without the bacteria, but like I said, it loses this defense capability so it's more vulnerable when it doesn't have its partner.
Sally: And who wants to live a dull, drab life when you've got the option of literally glowing.
Jamie: Well, I think it shows the importance - and this is why we use it and we study this symbiosis - is that symbiosis is so important for animal health and development in all animals. I don't know of a single animal that doesn't form some sort of positive relationship with bacteria.
Jamie: Our microbiomes are complex. There's many different species of them. So to understand what any given one bacterium is doing in our guts or on our skin or in our bodies is really hard to do. And that's why these partners, studying a little glow-in-the-dark squid is so important because there's just this single bacterium. This one symbiont living inside this one animal, so you can really tease apart the benefits and the interactions and the dialogue that's happening between the squid and its beneficial microbe.
Sally: Tell me more about this conversation. So how does it start? Are these squid born with these bacteria? Where do they get them from? Who's starting that dialogue?
Jamie: Right. So it's actually, the squid is born without bacteria and every generation of new baby squid have to acquire the microbes from their environment. And on the light organ itself, there are these little fuzzy arm-like structures that are covered in what we call ciliated cells, that brings in bacteria from the environment to the light organ. They're bringing in all kinds of bacteria. They're bringing it non-specifically, but they're looking for specific signals from the right bacterium.
Jamie: And the bacteria, on the flip side, they're just kind of floating around and they're shedding the outer part of their cell membrane or "their skin". And they're just secreting these kinds of molecules.
Jamie: And so when you have the right bacterium and the right squid, then you can actually initiate this conversation where the bacteria receives these shedded materials, these signals. They're called lipopolysaccharides. I know it's a big word for a sugar, but it's being released and received by the squid. And then once the bacteria have given the secret code, they actually are allowed to go into the light organ and travel downward.
Sally: Let's go a bit more specifically into this light organ. So it's a specific part of the body that has these light producing bacteria. Where is it? What does it look like? How big is it?
Jamie: So if a squid is about three or four centimetres long, it's probably about one centimetre in width, and it's bilobed. So there's like a mirror image. And the structure of this light organ is really unique. It's almost like an eyeball. It has all these little sacks where the bacteria live and then it's surrounded by what's called the reflector. It is a series of highly reflective proteins that can literally reflect the light and manipulate that. And there's all this musculature and a lens. And it actually acts almost like this eyeball-like thing. This is very unusual to particular group of... they're actually called sepiolids. They're not technically a squid, but they are very closely related. These sepiolids let's have this special organ.
Sally: Are you telling me a bobtail squid isn't actually a squid?
Jamie: I know, I know. That's where I...
Sally: We'll get into that another time.
Sally: One thing I know about animals and bacteria is we certainly have an immune system. Do squids have an immune system?
Jamie: Yes, they do.
Sally: So how does it not..? Like we spend a lot of our energy making sure that bacteria don't enter us and infect us. Whereas here it's got to deliberately pick out one specific bacterial species. How does it know which ones to accept and not accidentally get infected with something else?
Jamie: Yeah, that's a serious problem that people are looking at. We have bacteria that get to all the right places, too. And our immune systems aren't just trying to clear out every bacteria. So there's a learning process of what's health and what's danger. What is good bacteria and what is bad bacteria? And the body has to... all animals have to figure that out.
Jamie: These squid have these cells called haemocytes, which are, they're like little macrophages. They have the ability to go up, taste a microbe - literally they'll engulf a couple of them - and say, "Okay, do you have the right signal or do you not have the right signal?"
Jamie: And then if they have the right signal, then those haemocytes ignore that Vibrio fischeri for the rest of its life. So these haemocytes are constantly moving through the body of the squid as sentinels, trying to understand what's good, what's bad and keeping the bad guys away. And then what's interesting is the language that the immune system uses or a pathogen versus a mutualistic bacteria often uses the same language.
Jamie: And that is a big question in science, is what's the balance between health and disease? Where do you tip the balance and all of a sudden this becomes a pathogenic? Is it too much of signal A, is it too much of signal B? And that's something we're still in the process of learning.
Jamie: They're using the same language. They have the same words or the same vocabulary, but it's how they're constructing their sentences that is really what's defining whether it's pathogen or if it's a beneficial microbe. So the lexicon might be the same but the syntony of the words might be really different between a good guy and bad guy in terms of the immune system's perspective.
Sally: You catch the spy because it's doing a terrible accent.
Jamie: Yes.
Sally: And what happens to the light organ when all these bacteria have taken up residence?
Jamie: Those little ciliated, 'arm' structures, they die off. They've done their jobs so they undergo a developmental process and actually get lost in the squid and we just call it maturation.
Sally: Are they losing their little hairs, their little cilia because they're just getting older or is that in response to the presence of bacteria?
Jamie: If a squid never sees a bacterium and its life, there are some reports that they will stay, but that just doesn't happen in the natural world. I mean, it's only under artificial situations that some people have started to explore what happens when you don't have the right bacterial signal.
Sally: But that's really cool because it means that you've got this huge change in which genes are being expressed and which ones are being turned on and turned off just by the presence of a bacterium. So it's almost like a bacterial cell is influencing the genes of a completely different species.
Jamie: And that happens all the time. That happens, not just in this little squid, but in all animals and plants and fungi. Bacteria rule the world, really. They can play a huge role in gene regulation of all animals, other bacteria, other microbes, or eukaryotes, like plants, animals, fungi.
Jamie: So it is a huge paradigm shift in thinking of the importance that bacteria have had in the evolution, development and health of what we consider more complex organisms. But in the end, they are just influencing and controlling. And that's why I think we have got to spend more time understanding the microbiome and its full permutations.
Jamie: Right now, we know that people with diabetes, people who are obese, people who have all these other underlying health conditions have these unique composition or communities of microbes. And are they a product of the disease or are they causing the disease? And that is a huge question mark right now that people are just beginning to explore.
Jamie: Now that we have the tools, the DNA tools to go after all of these partners in these complex symbioses, we might be able to get a more complete answer to those kinds of questions.
Sally: And you mentioned earlier putting these squid in artificial situations. It doesn't get much more artificial for a squid than sending it up into space, which is something that you've been doing.
Sally: Okay, so squids in space. Why, Jamie? Why? Do they have little astronaut helmets? They're floating and round, chilling around. Why are you sending them up in rockets?
Jamie: I know that sounds very bizarre. Why would you take this aquatic organism and put it up into space where you would think that they're neutrally buoyant in the ocean, why would you expect any difference in the space environment?
Jamie: But to be honest with you, gravity informs all animals on the planet. We get directional cues. We're constantly at the mercy. It's the one thing on the planet that hasn't changed in four and a half billion years. So taking away gravity from the conversation is kind of a bioassay to understand new ways that bacteria and animals or how animals respond to different kinds of stress environments.
Sally: Because it's not something that they've evolved to.
Jamie: No, no.
Sally: They're not used to being micro gravity.
Jamie: No organism, no terrestrial organism is used to spaceflight.
Jamie: So I have two angles. One is I'm very interested in how astronaut health is going to be impacted by long-term space flight. You know, if you're an astronaut headed off to Mars and all of a sudden your Lactobacillus goes extinct halfway on the journey, is that going to be a problem? How are you going to mitigate that problem?
Sally: That's one of the key gut bacteria, isn't it, Lactobacillus?
Jamie: Lactobacillus. You might know that when you buy that probiotic yoghurt and you're eating it. That's why I say it. Cause almost everybody knows a little bit about Lactobacillus because it's very common in probiotics.
Jamie: So, if you're headed off to Mars, you know, are you in danger of something going wrong with your microbiome? So part of this question of understanding the dialogue and the impact that the stress of being in space - and it's not just micro gravity, it's also radiation, all of these things - how does that affect astronaut health?
Jamie: But there's a flip side to this. Everything we do in space really informs and helps us understand things on the ground. And one of those questions is, "What happens when you remove gravity?" Is gravity obscuring some new pathway or some new way that bacteria and animals talk to each other? And so that's the other side of this coin.
Jamie: When we remove gravity and give them this really novel stress, the animal doesn't quite know how to respond. So it starts firing off stress receptors and stress responses and all these things. And we get to see new ways that the bacteria are functioning. And so it seems silly to send squid up, but you want simple models that are easy to manipulate that are small, don't weigh a lot and can get you a lot of information in a short period of time.
Jamie: And that's why we send these little 'cephalonauts' into space.
Sally: I love that. So what are you doing when you're sending them up? What's a rough experiment like, because they'd going up to the international space station, the ISS. So what happens? Do you stick 'em in a test tube, send them up. What are you testing?
Jamie: We put them in little bags that have little connectors on either side that we can pump in new water, or we can pump in whatever we're testing, or we pump in bacteria. And we automate everything because astronaut time is rather precious. They're rather busy people. And then we can 'capture' the animals at certain time points across whatever experimental timeline we want. And then the astronauts can help us process and pack everything away and bring them back to us on Earth, and then we can go explore what happened during the experiment and capture that.
Sally: So you're looking right in that early window of these sterile baby squid getting these bacteria for the very first time.
Jamie: Right. We want to see how you start that conversation. So we were looking at zero hour, two hours, six hours, 12 hours; very early stages because the conversation happens fast. Genes turn on and off within nanoseconds. And so you want to be able to capture that - if the conversation's happening - fast.
Jamie: So we had done some ground experiments. We had simulated microgravity. This is another thing; way before you even get to space, you have to do a lot of planning and a lot of replicates of your experiment on the ground. So there's a lot of testing just to get this one little experiment off into space, but I understand why. It's important to make sure you're going to get good data from these very big initiatives.
Sally: And what data do we have? What so far has sending squid into space, told us about host-microbe interactions?
Jamie: Well, I can't go too in detail, but I will say that we're exploring the hypothesis that having your beneficial microbes is helping you modulate the stress response in space. So meaning when you don't have your microbes, so again, we were talking in an artificial situation, withholding the beneficial, microbes they actually on the ground show a higher stress response than when the animals have their bacteria. So the bacteria's kind of saying, "Hey, everything's okay. You can relax, you know."
Sally: It's like a comfort blanket for the squid.
Jamie: Yeah, exactly. You have your comfort Vibrios when you go to space.