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Transcript

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0:01Who are the characters behind science? This is Science Behind the Glass, illuminating the human side. In this podcast, we unveil the human side of laboratories and science. Scientists share personal experiences, and we discuss their meanings from different perspectives and fields of research. Disclaimer, this is a translated version using AI voice for the guest. Welcome to Science Behind the Glass, illuminating the human side. Today, we travel from the tropical forests of Costa Rica to high -tech laboratories in Australia to meet a scientist who has turned her childhood curiosity into a way of life. Our guest, Dr.

0:43Dani Rojas Asofeipa, grew up surrounded by biodiversity, fascinated by tiny creatures most people wouldn’t even notice, scorpions, spiders, insects. What looked like a mere childhood hobby became a scientific career that now seeks something incredible. medicines hidden in venoms. From a tropical scorpion to an Australian spider, Dani has followed the trail of compounds that could change the lives of people with epilepsy or heart problems. But her story isn’t just about science. It’s about migration, adaptation, and carving out a place as a Latin American woman in global research. How does venom become a cure? And what does it take to grow the world pursuing an idea? That’s the story we’re telling today. Dani, thank you so much for accepting this invitation. It’s a pleasure to have you here. Hello. Thank you very much for the invitation. Yes, it’s really lovely.

1:38I’m very excited. This is my first podcast. To begin with, tell us a bit about your childhood in Costa Rica. How did your curiosity for small animals like spiders, insects, bugs start? I think my family had a lot to do with it. I’m the youngest of five siblings. My brothers and sisters are much older than I am. So I always had a lot of freedom. My parents always let me wander, explore, do things, and I think that fostered a lot of curiosity in me. When I was little, I was always asking questions. I remember asking, what does this mean? A lot. Sometimes adults didn’t know how to answer. A few things about my childhood. I loved studying. I really liked school, strange, right? And I always loved learning. Maybe my focus on animals comes mainly from my parents, and my family in general. On weekends we’d go to national parks or city parks.

2:28We’d ride horses, visit volcanoes, and on the weekends we didn’t do those things, we’d go to my grandparents’ house. My maternal grandmother’s house was deep in the countryside. You couldn’t reach it by car. You had to park, walk along a little trail, cross a few rivers, and then arrive. I remember my cousins and I sometimes went on excursions, to the river to look for things, to see what we could find. All of that definitely influenced my decision to study biology later on. I liked all animals and nature, but I don’t feel that as a small child I was fascinated by something specific. That came later. I think the scientific curiosity really blossomed once I was in university. That’s a very interesting point and we have seen it in several interviews.

3:13Curiosity is the common thread and starting point for most scientists. It’s great and it pushes you to explore new things. In your case, what do you think sparked your interest in venom? I think it was my master’s degree. I finished my biology bachelor’s and then did a master’s in biomedical sciences. I started that master’s because I loved biochemistry, but I felt I was missing pure biology. By chance, there was an opportunity to work on a project at the Claudio Miro Picado Institute, which is internationally renowned for producing snake antivenoms. The project was very new. They said, we have some scorpion venoms. and we need someone who wants to start working with them. And that’s how I got into venoms. Before that I’d worked with spiders, mainly doing what’s called neuroethology, studying behavior from the nervous system perspective.

4:02In my undergrad I worked with a researcher at the University of Costa Rica. We wanted to understand biochemical changes in the brains of spiders, a species that was being parasitized by a wasp. I dissected spider brains, which were super tiny. So I started with spiders and then moved to the master’s project. Pure chance, but I loved it. Since then, there’s been no turning back. Oh, exciting. Can I know which spider species was it? No, it was Cyclosa. Wow, that’s very exciting.

4:34How do you evaluate the changes in the spider’s nervous system? Mainly with imaging, using antibodies to detect changes in the neurochemistry of what we call neuromodulators. And did you find differences when they were parasitized? Yes, there were certain differences. I don’t remember all the details now. It was quite a few years ago. But yes, some neurochemicals were being altered. And can you explain in very simple words for our listeners, as if you were explaining to a child, why you work with peptides and what those peptides are and why they are so important in the research you are doing? Peptides are like tiny proteins or little pieces of proteins. These peptides can modulate or change the activity of cells.

5:19Specifically, in my postdoc I’m working with epilepsy. We’re looking for peptides that can modulate neuronal activity. And you do this with venom peptides, right? Yes, exactly. Venoms in general are very complex. Spider venoms too. And inside them are many of those peptides that spiders use either for defense or mainly to hunt. The idea is to see whether any of these peptides, small proteins that evolution has fine -tuned to act on the nervous system of their prey, can be repurposed. or at least studied, to understand how they might affect the human nervous system.

5:52So we have projects not only on epilepsy but also on pain and heart disease. That was my focus during my PhD. That’s very interesting. And the animals you are using are Australian species, right? Right now, well, it depends on the project. Some are Australian. In one part of the project, we have venoms from spiders all over the world, and we do a screening. We test many of those venoms to see which one has the activity we’re looking for. You were telling us that you began working with these tiny proteins for disease research during your doctorate. What led you to do your PhD in Australia? How did you get there? Had you thought about staying in Costa Rica or perhaps doing a doctorate somewhere else?

6:33I ended up here because while writing my master’s thesis, I had to read a lot of papers, like any thesis. Whenever I really liked an article, I’d note the author. and it turned out that Professor Glenn King from the Institute for Molecular Bioscience at the University of Queensland was the common denominator. He appeared in every paper. I’d think, I love this it fascinates me. So I looked into his lab and decided to email him. He took a while to reply, but in my message I introduced myself, and said I was working with a scorpion venom at the Clotamiro Picado Institute. He answered, said he knew the institute, and wanted to have a meeting. We met, and honestly when I decided to apply for a PhD I said, it’s this PhD or nothing.

7:16I applied only for that scholarship, that doctoral program, and nothing else. If it wasn’t in that lab, I wasn’t going to do a doctorate. No plan B, plan B was, I don’t know what I’ll do. From the start I set several conditions. It had to be that lab, the venom lab doing drug discovery. It had to be in a beautiful, safe country where the PhD would be relatively short. compared with the US for example, where it can take many years.

7:42The doctorate had to be mainly research. I didn’t want to depend on teaching to keep my scholarship. I wanted to devote myself 100 % to research. I didn’t entirely manage that, because I still did some tutoring and small science -related jobs, but the main focus was research. And a bit outside the science box, I wanted to live somewhere with nice weather. Being a tropical woman, I miss warm beaches. So Queensland ticked all the boxes. Yes, your wish list came true.

8:11Completely. How lucky. You had already been working with venoms, right? Why do you focus on spiders? For instance, people have found drugs or active compounds from snake venoms. Why spiders? Aren’t the other arthropods candidate? I’ve always found invertebrates more interesting than vertebrates. I feel invertebrates aren’t studied enough. Whereas there’s much more research and information on vertebrates, it wasn’t about choosing the best venom. It’s simply that I like spiders more.

8:44Yes, I agree. I’m a bit biased though, but yeah, I love arthropods, especially spiders. Very interesting. You said the research focuses on these small proteins, the peptides. How do you identify these peptides within an animal’s venom? Have you already found a promising compound or peptide that looks like it could work for a specific disease? How does that part of the research work? First, you need a target. Usually these cellular targets are other proteins, large proteins, called ion channels. They let different ions pass through the cell and enable cellular activity. In many diseases, those ion channels are affected. So once we have that target, we want to see which venom acts on it. Often we need the raw venom to start. We go into the field, collect spiders, milk them, that’s the term for extracting venom, and once we’ve got it, we dry it, often repeatedly, and turn it into a powder we can use in various ways. We have cells expressing the ion channels we’re targeting and we screen the crude venom, straight from the spider, and run different assays.

9:54When we see a positive result for a particular venom, we take that venom and separate it into its main components. There are many laboratory techniques we can use, so we first separate the venom into its individual components. Once we have those many components, we retest them to see which one gives the activity we observed at the start when we applied the whole venom. Okay, assuming we find the ideal one, the next step is to identify the peptide itself. For that we use many tools, bioinformatics, sequencing, and so on. Because peptides are mini -proteins, and proteins and peptides are made of amino acids, we can determine exactly which amino acids make up that peptide. Once we’ve done that, once we know which peptide it is, we no longer have to go back to the venom. We can produce it in the lab. There are two main ways. One is to make it synthetically in a small machine, and the other is to use bacteria, yeast or other cells by inserting the gene for the peptide. The bacteria express the peptide. basically do the work for us, and then we can purify it. So it means that you don’t have to collect more spiders. Exactly.

11:05Unless we wanted to keep working with other parts of the venom, what we call other fractions, there’s no need. That’s really important, because to test a peptide that’s super tiny you need a lot of it for all the different analyses. And if that peptide eventually became a candidate for a drug, we’d also have to think about producing it in larger quantities. All of that matters when testing venoms. Whoa, that sounds super impressive. So much work. You also mentioned that you work with brain organoids to test compounds.

11:35You are not working with animals, but with these little organs instead. And you make them from humans. Could you explain a bit what is that? What the organoids are? and what is important, and I think that it’s great that you use them, but it would be nice if you could explain a little bit to our listeners. For this epilepsy project, many scientists are involved. Here in Australia and internationally, researchers, clinicians, specialists. It’s a very big project, and one of our collaborators is responsible for making these organoids. What are organoids? I call them mini -brains. It might sound a bit like science fiction, but that’s what they are. Clinicians have patients with epilepsy. These patients give blood samples, and we take the cells from that blood. Then we revert those cells to a primitive state, stem cells. And from those stem cells, we can differentiate neurons that are specific for each patient. And could you expand a bit?

12:35What exactly are stem cells? How do they differ from a regular cell? Say, when we cut our cells and the tissue starts to heal. Stem cells are basically cells that don’t yet have a defined destiny. Depending on the signals they receive, some can become heart cells, others brain cells, others skin cells and so on. They’re like baseline cells without an identity. Because they don’t have an identity yet, we can through different mechanisms, tell them to become neurons. If we add different factors, they’ll become heart cells.

13:08And that’s what I worked with during my PhD. Heart cells differentiated from stem cells. This gives us lots of advantages. First, we’re working with human cells. It’s often very hard to get heart or brain cells from a patient. You need many cells, so having access to these techniques and cell types lets us build very specific models. So in the epilepsy case, as I said, patients give a blood sample, we convert those blood cells into stem cells, and then we basically hack them and tell them, you’re going to become a neuron, a brain cell. We do that with a little group of cells, hence the nickname mini -brains, though the correct term is organoids. They’re not an organ per se, but a tiny organ -like structure.

13:49The big advantage in this project, huge thanks to everyone involved, is that the epilepsy patients we work with have types of epilepsy where different ion channels or brain proteins are mutated. Because those proteins malfunction, brain activity is dysregulated. That mutation information stays in the stem cells and transfers into the mini -brains. So when we apply the venom or peptides we think might help treat epilepsy, We can see the changes in the mini brain that are specific to that mutation for those patients. That is wonderful. It avoids using animals. Ethically, fantastic. And it’s very specific because these are cells from patients who already have those.

14:30Exactly. To be honest, eventually we will need animals. But the goal is to find the best peptide while using as few animals as possible. So first everything is in vitro. We do lots of analyses with the cells. Move on to these organoids. and eventually we would go to animals. And have you isolated any promising peptides or molecules, ones that have shown encouraging results for epilepsy? As I was saying, the epilepsy project is quite large. We have one peptide that has shown very positive results in these organoids and also in animal models. That part of the project is the most advanced. So yes, we have a very interesting peptide for a very specific mutation in sodium channels. We are now broadening the venom screening for other mutations in other channels linked to different types of epilepsy.

15:17In general, the epilepsy project began only recently, so we’ve been moving it forward this year. I can give you examples from other diseases where the main spider venom component has been successful. Australia is home to the world’s most venomous spider, the Australian funnel -web spider. From the venom of one funnel -web species in Queensland, a peptide called Hi1a was discovered. and it is very promising for stroke. It was first studied for stroke and later progressed to heart attack research. This peptide is fascinating. It helps rescue cells that have been damaged by a heart attack or a cerebrovascular accident. What the peptide does, its mechanism, is to protect the cell under the conditions that occur during a stroke or an infarction. Based on this peptide, my supervisor, Professor Glenn King, founded a Queensland -based pharmaceutical company called Infensa Bioscience to produce peptides like this one. It is also important for heart transplantation.

16:11There have been positive results there. And through protein engineering inspired by the funnel web peptide, even better peptides have been produced. All of this you are telling us is incredibly complex, right? And it’s fascinating to think it all starts with going out to find spiders in their habitat and seeing what their venoms can do. Tell us roughly what that field word is like and whether there is any way to know if the venom of one spider species might have more potential than another venomous species.

16:43Well, first, really, before going into the field, you have to read a lot, like everything in science. Pure reading. You have to learn about the spiders in the area, what is known about their natural history, and if there’s anything about their venoms. Then, in my specific case, I’ve gone to the field several times here in Australia to look for the funnel web spider. The species we’re most interested in lives on an island, the largest sand island in the world. There, instead of soil or regular sediment, you have sand. We go look for the entrance of the little burrow and start digging until we find the spider.

17:15Then we can bring those spiders back to the lab. A lot of it is trial and error, honestly. Many times there’s no information on the spider so we say, well let’s test the venom and see what comes out. and sometimes very interesting things appear, sometimes not. But yes, I’m particularly interested in Australian spiders because in Australia everything is weird, all the animals are weird, and super interesting. They all have their own superpower. Since Australia is an island, they’ve evolved that way. There’s also something interesting here. There are many venomous animals, so many.

17:48People say that in Australia everything tries to kill you, right Linda? I work with spider venoms, but I have colleagues who work with tick saliva. caterpillar venoms, plants, jellyfish. All those different venomous organisms are super interesting, not only from the viewpoint of making medicines, but also from a purely biological perspective. With all that excitement in your life, now I feel jealous. Let’s talk about your journey from Costa Rica to Australia. What has been the biggest obstacle you have faced as a Latin American woman and as a scientist? Something you would like to say has definitely been hard and how have you managed to overcome it? Yes, not everything is sunshine and roses. Like anyone who has migrated, there are always difficulties.

18:34When I left Costa Rica, I came in January 2020 and I didn’t know a pandemic was coming. Nobody did. I ended up on the other side of the world, in the middle of COVID, without my family and without knowing anyone. That was one of the first challenges. Then there’s the English. I speak English and have spoken it since I was very small, but Australian English is on another level. At first in meetings I’d tell my friends, I don’t know if it’s the English or the science, I’m not sure what I’m not understanding. And it’s not just understanding, it’s communicating. In Spanish I can be very fluent and use flashy words, whatever. In English I go, how do you say that?

19:14Sometimes I even forget the word in Spanish. I have to write down what I want to say. I always tell people. If you only knew how smart I am in Spanish, I’m smarter in Spanish. The culture is different. I think in general we Latin Americans share many things in common, so we could all say, oh yes, that happens in my country. Here everything is very different. Many things are different, though many are great, like being able to walk alone, safely, in the early hours of the morning. I could leave the lab at 1am and walk home. Cultural differences are many.

19:47So yes, as a migrant, everyone goes through that. As a woman scientist, something that always strikes me, and maybe this isn’t just in Australia, is that science still seems to be a man’s world. No offense, Daniel. None taken. That’s the truth. Most senior positions are still held by men. Almost all my collaborations were with men. So sometimes I’d have to present things in a meeting, say on Zoom, with collaborators. They were all men, all white, native English speakers, some Australian, some American, and it was impossible not to feel intimidated, despite the fact that they’re wonderful people. My advisors too, both my PhD and postdoc supervisors are men, are great human beings and brilliant scientists, but that didn’t stop me from feeling intimidated. I’d tell myself, I have a meeting with six men, all speaking perfect English, perfect science, and I felt I had to prepare, have a little tea beforehand, and the meetings always went fine. They’re really nice, pura vida, as we say in Costa Rica. When I noticed that, I tried to seek other collaborations.

20:49Honestly, I found a few. Of course there are other women in science, so we worked with them. I always tried to have at least one woman on my PhD committee. I specifically asked for that. As for English, I’m still working on it. My partner is Australian, so although we can speak Spanish, we always communicate in English and he helps me with words and phrasing. Reading a lot in English helps. and encouraging other women too, it can be done. It’s curious that the top positions are still mostly male, even though there are many women in science. When I hear that, I say, I’ll stay here longer to prove it’s possible.

21:24I also got involved in outreach. During my PhD I was a science ambassador for the institute, explaining science, going to schools, talking about spiders, I could talk about spiders all day. It’s about showing the world that someone from a developing country can do it too. And to finish up, the diseases you say could be treated with these compounds have a very high impact on the patient’s life quality. How do you think it impacts patients to have people researching and developing this treatment? These diseases, neurological and cardiac, severely affect patients’ quality of life. As I said, this is a huge project and interdisciplinarity is vital. We work with many researchers across Australia, with clinical specialists, and something I find very interesting.

22:09with NGOs. The epilepsy -related NGOs in Australia and the US were founded mainly by parents of children with epilepsy. So you learn not only the science but also the emotional and physical burdens of living with epilepsy. Epilepsy affects a million people worldwide, and not all forms have treatments. Some are very severe. The spectrum is huge. Pediatric epilepsies can hinder development. We usually think of seizures, but behind them can be cognitive delays. Some patients don’t live long lives, and there’s a heavy emotional load. My hope is that by designing these therapies, we can make epilepsy more manageable, targeting forms with no treatment, with fewer side effects, helping patients day to day, and also easing the burden on their families. Dani, what you do is awesome. Thanks for sharing all your experiences, challenges, and knowledge in simple words. Thank you. This episode was inspired by the web that connects us with our natural world. Despite myths and stigmas, when we look beyond fear, we find ancient astonishing animals that teach us about adaptation and resilience. Our journey with Dani urges us to see past myths, the unknown, and fear, always guided by curiosity. Of the more than 53,000 described spider species, only 25 pose a real risk to humans. This means less than 0.05%. making widespread fear a disproportionate myth. Their venoms, on the other hand, have yielded

23:42more than 1,600 peptides with therapeutic potential, and millions more may await discovery, ready to ease pain, to stop arrhythmias, or protect hearts, like the promising HI1A peptide from the Australia funnel web spider. But venom isn’t their only superpower. For 380 million years, Spiders have been invisible guardians of balance, devouring up to 800 million tons of prey each year, controlling pests and recycling nutrients.

24:15In their smallness, they teach us resilience and efficiency, virtues as valuable for nature as for medicine. Science Behind the Glass is an independently produced and edited podcast by hosts Linda Hernandez -Duran and Daniel Sguerra. with invaluable technical support from Rafael Giordano and original music by our colleague and friend Bernardo Aguilar. Follow us on Instagram, X, Facebook, LinkedIn, and TikTok. And visit our website for more stories, resources, and updates. If this episode inspired you, share it with your communities and your friends. And consider supporting us via PayPal in the button Support Us in our webpage. Your contribution will help these narratives keep growing. Remember…

25:00Innovation is born where wonders meet curiosity, and sometimes where a tiny spider waits in its way. Until next time.