In this episode, Patrícia Ferreira, (she/her) a PhD student in the Department of Biological and Chemical Sciences and 2022 WinS Hypatia winner, explains that not all animals have a stomach. Her research explores why the stomach evolved and tries to explain what it does. Her research uses the power of CRISPR gene editing to create fish that have no stomachs and then uses these animal models to explore why organisms have stomachs and what the implications are of having a stomach, or not.
The episode features:
WLU Research Chat S03 Patrícia
Unknown 00:00
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Shawna Reibling 00:04
Welcome to the third season of Research Chat. In this season graduate students share the challenges of their research work. In this episode, Hiro will interview Patricia. Let me introduce the participants to you. Hiro Kato, who uses pronouns he/him, is a third year PhD student in the mathematical and statistical modeling program offered by the Department of Mathematics at Wilfrid Laurier University. He is working under the supervision of Joe Campolieti and Roman Makarov. He completed a Bachelor of Arts in economics and financial mathematics at Wilfrid Laurier University and a Master of Science in Mathematics also at Laurier. His research has been supported by multiple awards, including the Ontario Graduate Scholarship, and the Queen Elizabeth II Scholarship. Patricia Ferreira, who uses pronouns she/her, is a comparative physiologist who is pursuing a PhD in biological and chemical sciences at Wilfrid Laurier University. To address her research questions. She creates knockout models in fish, and previously in mice that target specific genes/proteins to better unveil their function and mechanisms of action. She has been awarded two Ontario graduate scholarships, and a Hypatia award for women in science from the Laurier Centre for Women in Science. She holds a bachelor's degree in biology and a Master's of Science in Marine Sciences from the University of Porto in Portugal. Thank you to you both for speaking with me today. I will now turn the microphone over to you.
Unknown 01:41
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Hiro Kato 01:47
Hi, thank you for chatting with me about your research today.
Patricia Ferreira 01:52
It's my pleasure.
Hiro Kato 01:54
Can you tell me about the research group you're a part of, and how your work fits into research program?
Patricia Ferreira 02:01
Yeah, of course. So it's actually started back in 2014, when I started working at Jonathan Nielson, still in Portugal. So him and another researcher Philippe Castro, also from Portugal, were very interested in the paradox of stomach loss in vertebrates. This, simply put, means that they were very curious as why did some animals lose their stomach during evolution? And so I went to Jonathan's lab, to do my master's and that topic of stomach loss. And the current project I'm working on is yet another piece of this very, very complex puzzle, to understand how important is the stomach? And what happens when we lose it?
Hiro Kato 02:45
Sounds interesting. What issues or questions do you plan to explore in your research?
Patricia Ferreira 02:52
So I would say that a good starting point is that we know that the stomach is important - that is known. So when animals first evolved to have a stomach, so when the stomach first evolved, the animals gain this great advantages of an additional digestive organ, and also a very nice barrier against bacteria, and so on, because the stomach produces acid, and people might have felt this acid reflux in their lives. So this acid actually helps by killing microorganisms. So quite a nice advantage, right? But even though we know that it is important, no one has actually quantified exactly how important this organ is. You see, when we look at digestion, we are looking at the teamwork. The intestine does the majority of this work, but it seems that all of the digestion relies also in very important feedback mechanisms from the stomach. So we decided to see exactly how much the stomach does. And the best way to see how something is important in my perspective, is to take it off to shut it down or turn it off and see what happens. So just imagine, for instance, that you are in a room, and there are several lightbulbs. And I ask you, is that lightbulb over there needed? Well, we turn it off, and we see what happens, right? And that's exactly what I tried to do. So I go into the lab and I shut down the stomach. I turn it off, and I see what happens to that fish.
Hiro Kato 04:17
Are there any animals out there that don't have stomachs? And how do they fit into your research?
Patricia Ferreira 04:24
Yeah, for sure. There's a whole lot of animals that don't have stomachs. They're more common than you might think. Actually, if anyone that's listening has a goldfish, they can now know that they do not have a stomach. Other models that are actually commonly used in biomedical sciences there's zebrafish, they don't have the stomach, and the platypus you might have heard of it. This mammal that lays eggs, they do not have a stomach either. So there's actually quite a few there are mainly fish but there's the platypus is a good example, as a mammal example of an animal that doesn't have a stomach. How do they fit in my research? That's that's actually one of the reasons we created this knockout. Because we wanted to know what happens when an animal doesn't have a stomach? That's our main question because we've been quite interested in that stomach loss, why do animals evolved to have a stomach and then they ended up losing it? It's kind of a paradox. And when we tried to address this question, looking at these agastric, so at this animals that do not have a stomach, we are left with a whole lot of confounding factors, because we might be comparing a goldfish that doesn't have a stomach and looking at how it digests and we are comparing it to a salmon or a trout, we are looking at a trout that has a stomach, and we are comparing two different species. So okay, one has a summer, the other one doesn't. But there's so many other factors that might be confounding us. And that's why it's so important to create the knockout model, because in the same species, we'll have some animals that don't have a stomach, and we have some animals that have so our controls. And it allows us for this very direct comparison, there's no other differences - some don't have and some have. So it is, as you were saying, you use models in your work, that allow you to look at a specific situation and address it, I create these models also to look at this specific target, in my case it's the stomach, and address a very specific question with nothing else confounding.
Hiro Kato 06:29
That's fascinating. So can you tell me the key features of this model that you're creating in this lab?
Patricia Ferreira 06:35
Yeah, so we use a technology, it's called CRISPR, Cas9. And what I did is, I go and I genetically alter this organism. So I have a fish and I'll change a little bit of its DNA. So it wants to be able to produce a protein. And this protein is very important to these little molecules. So it's important to create the acid in the stomach. So the animal wants to be able to produce this acid. So if there's no acid, there's not a functional stomach, the stomach is merely a bag not doing really much, and we can see what happens in the intestine. So what happens downstream.
Patricia Ferreira 06:41
What challenges have you faced throughout your research?
Patricia Ferreira 07:23
I would say that this is an ambitious project, it's quite hard to create novel genetic line, in such a short time period, a very short period of time for years to create, not only the model, but we also need to see to experiment on it, and to describe it to see what happens. So that's for sure one of the challenges. Obviously, we need to put all of this also in the context of a pandemic. So I started in 2020 and then we have very long lab closure due to the pandemic. So it gave us a whole lot of new challenges to address. But it has been quite interesting journey overall.
Hiro Kato 08:05
Thank you, and I'm sorry to hear about the lab closure. Could you tell me the next step in your work?
Patricia Ferreira 08:11
Yeah, for sure. So right now, we have the first generation of mutant or transgenic fish, if you will. And in this first generation, only some cells are turned off. So we still have some acid secretion in the stomach, the stomach is still able to digest. So what I'm doing next is, I'm going to cross these animals until I get a full knockout. So that means that this next generation of animals, all cells in the stomach are going to be turned off, so they won't be able to produce any acid, and this means that the fish will be a full knockout.
Hiro Kato 08:51
Thank you for giving me the outline. How would you place your research in the context of different study areas beyond fish studies? Do you think either researchers would benefit from the results of your work?
Patricia Ferreira 09:05
Yes, so first of all, it is out there, once we create this model science is all about collaboration, right? It's about putting something new out there that goes beyond whatever we thought when we created the model. So people can use this new genetic line to address different questions. And for instance, there has been people looking at the impact of anti acid so those drugs that people can buy at the pharmacy and take when they have problems, gastric ulcers, and so on. So, researchers have been interested in seeing what happens when people take this or what happens when other animals take these anti acids. And so there are some results pointing to the possibility of this anti acids impacting growth, because there's an obvious impact to nutrition and so in the absorption of nutrients that will help the organism, the animal, grow. And there has actually been an interesting work where scientists show that these anti acids may reduce the ability of the body to get magnesium and we know that magnesium is important. It's important for our brain function, for instance, you might have heard of people taking magnesium supplements for the brain. So it's quite interesting that a series of pathways downstream in the test, may be impacted when there's no acid. So other researchers can just get our model and address these questions. There's an unlimited potential, I would say, to this dismal loss in whatever way they want.
Hiro Kato 10:37
What should people remember about the topic? Or what would you say the take home message would be of your research?
Patricia Ferreira 10:45
Well for sure that the stomach is important, we know that we feel it tells us that we are hungry. But next time people feel sleepy after eating, they may remember that it is because of this complex process that digestion is. The stomach is definitely important. But not all vertebrates have stomachs, yet they still eat, they still live, they still grow. So maybe it makes us wonder organisms that don't have stomachs have special adaptations to help them compensate for this. And where do we find this adaptation? So yeah, that'd be a nice take home message, I would say. There's a world out there that we are aiming to unveil, and it will help us answer this question for sure.
Hiro Kato 11:31
Is there anything about your research that you feel is important to share?
Patricia Ferreira 11:36
Yes, I oftentimes think that we should emphasize more that even though the creation of transgenic animals and plants for that matter, is oftentimes seen as something that's coming from a sci fi movie, or something dangerous, it can definitely bring us new ways of solving open questions in science. So maybe we should embrace some of this technology as an opportunity to solve very important and relevant questions that are out there waiting to be solved.
Hiro Kato 12:04
Can you provide a definition of transgenic or knockout animals?
Patricia Ferreira 12:10
I think in a very simple way, we can say that this transgenic or knockout animals are animals that have targeted mutation, something that we want to control. So something that we want to study, and we target that. And we as researchers, we oftentimes choose to turn it off. Because if we create a knockout model, or a transgenic that does not have that specific part that we are interested in, it will allow us to further investigates the impact of that protein, of that gene, of that piece of DNA in the whole organism. So they are just animals or organisms that have something that's been plucked or switched off.
Hiro Kato 12:57
Will this research helped people who have had their stomachs removed, or who have less stomach acid?
Patricia Ferreira 13:04
Well, it's kind of a long way. So we are starting with what's called fundamental science, you're creating this first model, and it's a fish. So it's quite far from a human still. But one of the ways to address this question is actually looking at it from a comparative physiology perspective. And in that perspective, yes, along the way, and it's not going to be next year or five years but, one day, these fundamental science findings might be translated. And that's when we get in and translatable science from fundamental to the translatable part. So yes, they can one day be used to address problems or potential problems that people in proton pump inhibitors, so this anti acids, or that have had their stomach revolts, problems that might arise from that, for sure. But there's still a long way to go to them.
Hiro Kato 14:00
Thank you for sharing your research with me today.
Patricia Ferreira 14:04
Oh, thank you also. It was very nice speaking with you.
Shawna Reibling 14:07
Thank you to you both for chatting about your research. Whether you're exploring the role of the stomach are determining derivatives prices. Models are very useful ways to experiment and predict what may happen based on data and testing within models
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Shawna Reibling 14:29
I hope listeners enjoyed listening to today's discussion and learning about using models to understand both finance phenomenon and the role of our organs. If you'd like to learn more about these topics, there are resources, additional readings and details about the work of each researcher on our website wlu.ca/research-chat. Listeners like you are encouraged to share these episodes and use these podcasts to discuss these topics with your friends or as an assignment in the classroom. Subscribe on your favorite podcast platform to be notified of new Research Chat episodes. Research Chat is a partnership between the Office of Research Services, the Faculty of Graduate and Postdoctoral Studies and the Laurier Library. Thank you to everyone who's contributed to the creation of Research Chat. A gratitude list can be found on our web page.
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