For my stories in Nature Methods on model organisms, Model organisms on roads less traveled and Models and career-makers I interviewed Paola Oliveri at University College London. And here is a podcast based on that conversation as well as as transcript. You can find this podcast in the series 'Conversations with scientists' wherever you stream podcasts. And here.
Note: These podcasts are produced to be heard. If you can, please tune in. Transcripts are generated using speech recognition software and there’s a human editor. But a transcript may contain errors. Please check the corresponding audio before quoting.
Vivien Marx Hi, welcome to Conversations with Scientists. I'm Vivien Marx.
All echinoderms are marine organisms. So echinoderms have done an enormous amount of novelty and so to understand, including, you know, completely reshaped their body. The body pattern from bilaterial to pentaradial, which is absolutely dramatic.
Vivien: That's Paola Oliveri, a researcher at University College London, talking about echinoderms, which include marine organisms such as sea stars and Brittlestar SARS. What's dramatic about them, they don't just have two legs, they have five limbs. They are pentaradial. And when a predator tears off one of the brittlestar SARS limbs and these organisms escape, they can regenerate the lost limb skeleton and all how this evolved and how this regeneration works or some of the questions she studies.
You will hear more from Paola Olivieri and about her in this podcast. Just briefly, let me tell you about this podcast and we'll get right back to Brittlestar, SARS and seestar's evolution and novelty. In my reporting, I get to talk to researchers around the world, and this podcast is a way to share more of what I hear. This podcast takes you into the science, and it's about the people doing the science. You can find some of my work, for example, in Nature journals, where working scientists publish papers about the latest aspects of their research.
In a number of these journals have science journalism with pieces by science journalists like me. Yes, this podcast is about animals and experimenting on animals, which I know some people are opposed to. And yes, animal experiments are uncomfortable to consider. But please give this podcast a listen. It might offer some aspects that you might not have heard about yet about the value of doing ethically responsible research with animals. Paola Oliveri is a developmental biologist and she studies organisms to learn how a fertilized egg becomes an embryo and then a pentaradial organism.
She looks into how organisms evolve and change, where and how novelty arises. And she teaches biology. As is true for so many scientists these days, COVID-19 has affected her ability to do research, but it has also made her proud of science and the progress in genetics that has allowed scientists to wrap their heads around SARS CoV-2 the virus that causes COVID-19.
[2:37.] - Paola Oliveri
The possibility, the diagnostics, the possibility to sequence this virus so fast. I sat back a little bit. Then I thought, you know, if the same thing happened 10 or 20 years ago, it will take us much longer to identify what was going on, to figure it out, to modify, to engineer. We know so much about how the immune system works and we also have a lot of things that we don't know. But you know how we have done, fortunately, many different vaccines. We eradicated some diseases completely. So we know quite well the dynamic in the population and the molecular aspects and cellular aspects. I mean, it's fantastic.
Vivien : Paola Oliveri teaches biology and evolution and an appreciation for different organisms. Not all of her students want to go into research and not everyone is interested in a echnioderms. But she's trying to convey a sense of an understanding of how evolution has shaped the natural world.
The students in biology, from my experience here at UCL in the UK, I would say that they are divided into major streams: a stream that goes into science because they want to they are interested in advance of science and knowledge. And I don't think they will be, this makes them difficult going to work with Drosophila or sea urchin. They are more looking for what are appealing questions to them. And they continue. And actually they are the ones that may end up even doing, you know, very weird new animals or things like that.
Then, of course, there are, which I'm not saying that they're little, but there are another part of the biology students that they are much more driven on. I would say the biomedical aspects. So biology to solve human problems. And then certainly, yes, I would say that potentially they will not, they might have an experience into echinoderms, but they're not definitely they're not going to be their favorite.
In speaking with students and reading their papers and assignments, she realizes it's important to think carefully about the words used to describe science.
[5:14] - Paola Oliveri
You know, I teach--this is my teaching term--and so I get a lot of write-ups from students and all these things. And I deal a lot with evolution. One of the things that I say to my students, there is one word that I'm starting to become a bit allergic when they write, which is not wrong but is which is the word believe. Because it is interpreted wrongly by the others. It's not that I believe, I have some evidences and this is my model.
It's not just a blind belief that this is what happens and that's the biggest difference. And then I say, you know, maybe we should start to refrain a little bit to use this word in scientific context and to say the things in a little bit more correct way, you know. Because in reality, the word has a different meaning. I mean, it's used in normal life, in many different contexts. So some people might misunderstand how it is used in that context.
One aspect that fascinates Paola Oliveria about echinoderms is that they can regenerate. And that is an aspect that caught one of her students, rather, by surprise.
I had a student, an undergraduate student that is, just to tell you about the experience, she was very much interested in regeneration, per se, and she had she was in the stream of human genetics. So nothing more than having that way of thinking. And when she was assigned to me for a research project, she was a bit disappointed. But, interestingly enough, and that is about perception, after not even a month, not only she graduated, she did a bachelor with me, she did the Master's with me, and she did the PhD with me.
And she actually is the person that I need to thanks to basically open up and put the hands about this, started to work with the regeneration in echinoderms and try to compare with development and try to disentangle how much of the developmental process is used or reused during regeneration. How much is new? Is regeneration specific? And tried to figure out how the two things.
So she was a human geneticist. She just in the reality is many people actually don't even know that, that you can do so much important advancement in these systems.
Vivien: Her student changed her views just by working with Paola Oliveri and realizing how many basic biology questions this organism would help answer.
[8:08] Paola Oliveri
We work together, beautiful, it's fantastic. Is nothing better than. Of course, I have my knowledge, my experience on the system. We look together. What was the best system that could worked for where we were? And this is where all the things were already published on a descriptive level. And then we went to the marine station every year for summertime to collect these animals, to do the experiment, to try to do controls and no controls.
And that's how it came came out beautifully, to extract DNA, to sequence the genome, to do transcriptome, to really get an advance. Of course, all these things are done in a mouse. So if somebody only wants to do, you know, divine methods and that is important for, nowadays, for the coronavirus and things like that certainly it's not as fast. But that doesn't mean that it cannot work and that doesn't achieve important advancement.
To study basic biology questions, Paula Oliveri feels she has found the ideal organisms to study. They are sea urchin seastar and brittlestar. For a long time, there's been a kind of pantheon of so-called model organisms, the ones many scientists study and are supposed to study.
This pantheon includes the fruit fly corn, the nematode, the mouse, among others. Historically, in developmental biology, sea urchin has been an important model organism. Alejandro Sanchez Alvarado, who is executive director and chief scientific officer of the Stowers Institute for Medical Research, and he's a Howard Hughes Medical Institute researcher, he thinks that the time has come to dispose of the terms model and non-model systems. He prefers a term that he finds more accurate. That's research organism.
Paola Oliveri did postdoctoral research in the lab of Eric Davidson at Caltech, the lab's research organism was sea urchin.
[10:22] - Paola Oliveri
Before, I was only working with sea urchin. And when I was in Eric's lab, I was always only working with sea urchin. But now and you sent me a quote from Alvarado Sanchez about model organisms, and I can only agree with him. Now that we have the genomes, now we have the things doesn't exist anymore an model organisms. So we can expand our approaches to various classes. So what I introduced, since I am at UCL, is a species, which is actually a brittlestar, not a seastar, which is very interesting for me, for the dual aspect.
One is the evolution of one cell type, which is how these animals make the skeleton in the larvae, but the other interest is: they regenerate. And so the beautiful thing. They have both the development and the regeneration available. So one of the things about model organisms that nobody tells you until you put something could be a model organism for regeneration, but they cannot do any embryogenesis on that or vice versa. It could be a wonderful embryo developing things, but you cannot have it to work.
And that is really when I teach to my students. The reason why you say: they don't exist model organisms, there exists experimental organisms that we need to use properly, depending on the questions that we want to ask,
The pantheon of model organisms, the one that so many have studied in the past, they don't appeal to her for her research. They were the organisms to study a small group of important, big-shot organisms.
[12:14] Paola Oliveri
Yeah, they were, because, it's a very old-fashioned way of thinking, which is, I think I'm very much convinced it's hard to die. And the reason behind model organism is: when the tools were not available, the genomes were not known, the genome editing was not available and all these things, these were the only animals that in the lab could have been raised in a fast way, we could have done genetics and all these things.
But to be honest, I mean, now, with all the advancements that we are doing, we are next-generation post-post next-generation sequencing era. We can sequence everything very cheap. I mean, in UK, the Wellcome Trust launched the Darwin Tree of Life. We want to sequence sixty thousand species around UK. So you can imagine what is the knowledge that we have now? Do we really need all these old fashioned genetics? No. We have genome-editing and all these things, so we can start to do experiments rather quickly in many different species and many different things that might be much more appropriate actually, to answer some questions in science.
These days, Paola Oliveri splits her time and attention between sea urchin and Brittlestar
[13:36] Paola Oliveri
I split time with the two, because I'm also interested in the comparative aspect, which is another thing that sometimes working only on a model system, you lose the. So you think that everything happens in that model organism is the truth. But it could be a specialty of that model organism.
For example, much research has been devoted to gradients that develop in embryos and they shape how the body plan is laid out. There's one called bicoid, a gradient in fruit fly embryos.
[14:10] Paola Oliveri
I just want to make a very simple example. Have you ever heard about bicoid the gradient?
From fruit flies? Yes.
[14:18] Paola Oliveri
So that's been such a model of gradients. I mean, an enormous amount of, I mean, I'm not saying that it was not important, it is important, but an enormous amount of scientists work on this problem and problem of these gradient and all these things. But in reality it's a specialty of Drosophila. As soon as you look at other insects, they don't even they don't even pattern the body using bicoid.
So this is one of the things that by working only on your model organism you actually missing, you're missing the perspective of what really is in common and is essential for all living organisms and what is actually a specialty of your system.
What also fascinates her is how change has evolved. We all have a common ancestor and from that ancestor, all of our planets' animal diversity has evolved
[15:13] Paola Oliveri
So during evolution, think about it, we all come from the same organism that's in. There's the Cambrian explosion. There have been an explosion of diversity, but we all come from the same organism. So in order in evolutionary terms to go from, let's say, an ancestral of chimp and human and to create human and chimp, you need to change certain things.
You need to rewire the network. You need both in development and physiology, in gene expression and all those things. So this constantly happens. So to disentangle.
Of course, is very hard to work with human and chimp for the timing being, for various things. While it is might be very easy to do, for example, with echinoderms, where we have many different animals that. We can have the embryos, they develop really fast, like three, four days, they're very easy to explore.
Now that we have the new modern genetics and so we can explore the brittlestar, we can explore the seastar, we can and we can start to compare and to understand how morphology can change because we change certain parts of the DNA, certain parts of the regulatory network, and what are the important parts that they are. Because not all the change will be successful. Some of the changes will be terribly deleterious. So what happened?
There's a special role for understanding evolution, what aspects organisms have in common. For example, Hox genes specify which part of an embryo will give rise to an animal's head in which its tail end. Beyond these issues are the issues of novelty, the things that make some animals very different from others. Here's Paula Oliveri.
[17:02] - Paola Oliveri
In the past, because we knew very little, we knew very little genetically. We knew very little about genes in general, people were trying when they were doing evolutionary studies, to identify what was in common, Hox genes and all these things. Now, in a way, it is extremely established. But on top of that, evolution is not only what is in common, of course it is what is in common because we come from the same organism. But it's also about novelty.
So how can we generate novelty? How can we be different in many different ways? So echinoderms have done an enormous amount of novelties. And so to understand, including, you know, completely reshape their body, the body pattern from bilaterial to pentaradial, which is absolutely dramatic.
Now that we have a lot of things in terms of we establish what are the genes that they're always being present in, what are the toolkit and all these things, so how can we generate this novelties? So now that we have so many things in common genetically, how they can do that?
Brittlestar, A. filliformis / Oliveri Lab, UCL
To do this work, scientists use a variety of tools, such as gene editing. That includes CRISPR, base editing and other approaches.
CRISPR works, CRISPR works also with some other modification. There have been, I think is just single-base editing. And of course we have other tools in terms of knock-out, knock down.
Of course, the transgenesis has been done with Eric, I would say probably I don't want to say older than me, but I know it's not older than me, but it's certainly 30 years and more that we can do transgenesis and things. So to study. And actually in terms of the genome, I mean, you put that the the experiment of the pro-nuclear fusion, but also the chromosome theory as being developed by Boveri, the hereditary chromosome theory was by looking and working with sea urchin.
Cycling has been done working with sea urchin. That's what I would say, basic, big, basic understanding. The sea urchin lended itself beautifully for doing all of these discoveries. But the genome in particular, it is a very good point.
On top of that, for example, you mentioned C elegans and Drosophila. From the genome point of view, c elegans and Drosophila are actually going back, they're very old. They have less genes. They have very compact genomes.
There are very, they are not even reflecting while the sea urchin has a genome that is much more typical of an animal genome with large genes, big intergenic regions. And all this. Of course, again, in all the situations, there are advantages and disadvantages.
But the question is, do we want to see how like a big genome evolves? I wouldn't work with Drosophila or C elegans. Fortunately, the genomic technology has been much more democratic than the model system.
So they're being applied so easily to everything. And and I'm talking about next generation sequencing, single-cell sequencing, all these advancements and these things, so it becomes much, much easier to understand what is the beautiful?
Paula Olivieri looks at genomes, but not, for example, to find what change might be associated with disease, which is the way, for example, cancer researchers study genomes. For her, a genome is a kind of readable time machine to explore how evolution took place.
[21:18] Paola Oliveri
I feel myself very much a developmental biology. My training is in developmental and cell biology. One thing that always fascinated and is a little bit part of what I keep doing is the evolutionary aspects. So how we have this beautiful diversity of life on Earth and how did it really emerge and what are the mechanisms?
And but I'm always thinking very much in molecular mechanism: how these things happens. So I'm not so in a way, I'm not very much interested about the nuances of population genetics or variation and things like that, but much more on how really, by looking at the genomes, we can see what really happened in time and how major transition can happen.
Can we? There was beautiful discussion we always had with Eric. Can we have, you know, a co-option, large, complex characters in one context versus the others?
Are these things can happen in a short amount of time, in a long amount of time. Can we see this in the genome? So can we use all the genetics, the beautiful advancement that we are doing in science? You know, there are all these genome projects, so they're coming where we are sequencing genomes after genomes.
How can we use them? Can we use them to understand better how nature rewired the whole development in order to make something new. These are very basic and fundamental questions.
Paula Oliveri always enjoyed basic research, and especially so during her 11 years at Caltech, where she worked with developmental biologist Eric Davidson who passed away in 2015.
[23:14] Paola Oliveri
It has been a fantastic, absolutely fantastic experience. I really enjoyed to work with Eric. He was. I mean, personally, he was a kind of a potentially controversial figure, but certainly absolutely brilliant.
And to be working with him it was really amazing. I learned a lot of things also in the style of how to mentor people. So how to, you know, discuss science. I mean, of course, science was always the important thing, but what are the, you know, how to go into science and how to walk in a path that nobody ever walked before and not just be afraid.
I mean, just, you know, open the wings and fly and just get creative. And that was really a fantastic experience and mentorship for me.
Learning how to walk where others have not walked takes courage in any area, and especially in science.
[24:20] - Paola Oliveri
It is scary, of course, but at the same time, you know, actually thanks to him, the enthusiasm was reborn in me. It's very interesting. My history, I come from Italy, I did my PhD in Italy. At the end, I was at one point bit puzzled. I was like any person we all got into some deeper crisis and I didn't know if I really wanted to take research seriously and continue or or do something else with my life.
And I just said, well, let me let me try the postdoc with Eric. I had the opportunity, I was accepted and I said, let me try. If it doesn't work in a year, I said to myself, I'll just start go to do something else. And he completely refired the enthusiasm and love for science and for research.
To Paola Oliveri, traditional organisms used in research show a bit of a bias toward land-based organisms.
[25:33] Paola Oliveri
If you think about all the model organisms are land organisms, because in a way we live in land and we think. Somehow I think there is also kind of like, we feel more related to them, we understand that we are, no matter what, we have seen many insects. So we think we we believe that we need to relate to things in a better way. We understand better. I would say, in common imaginary, therefore, in what you are choosing to study.
But the reality is, a lot of ecosystems, marine ecosystems in this world and has an extremely important. There are a lot of species in there and it has an extremely important value.
Probably things will change a little bit because we, hopefully, will understand that human health means also ecosystem health, world health.
Therefore, people will start to have the tendency to have a little bit more an holistic approach to solving what is human problems or things like that. And not just means: is a disease and we need to cure it, but a more like ecological approach, conservation approach and all this things.
That was conversations with scientists. Today's episode was with Dr. Paula Oliveri from University College London.
And I just wanted to say, because there's confusion about these things sometimes University College London did not pay to be in this podcast. This is independent journalism produced by me in my living room. I'm Vivien Marx, thanks for listening.
Brittlestar, A. filliformis / Oliveri Lab, UCL