NATURE PODCAST

Podcast: RNA splicing in yeast, and a walking fossil

Benjamin Thompson and Charlotte Stoddart bring you the latest science news.

This week, investigating introns’ roles, and reanimating a fossil.

In this episode:

00:52 Predicting a prehistoric perambulation

Researchers have used multiple techniques to figure out how an extinct animal might have walked. Research Article: Nyakatura et al.; Editorial: Cinematic and scientific techniques combine to show how a long-extinct creature moved

07:29 Research Highlights

Crows making inferences, and a long-lived supernova. Research Highlight: Clever crows size up objects blowing in the wind; Research Highlight: Zombie supernova finally snuffs out

09:31 Splicing for cell survival

A new role has been suggested for excised RNA sequences. Research article: Parenteau et al.; Research article: Morgan et al.

15:27 News Chat

A science funding shake-up in Serbia, and crowdfunding winners. News: Serbia is rethinking science — but the reforms could cost hundreds of jobs; News: Crowdfunding research flips science’s traditional reward model

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Transcript

This week, investigating introns’ roles, and reanimating a fossil.

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll be finding out how a fossilised animal walked.

Host: Charlotte Stoddart

And hearing about a potential role for the so-called ‘junk DNA’ within genes. I’m Charlotte Stoddart.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

Somewhere around the late Devonian era, perhaps 360 million years ago, vertebrates started to invade the land, dragging themselves out of the water and expanding into pastures new. The first land invaders were likely to be pretty hopeless at moving about on land but as time went on, terrestrial creatures would evolve, developing ever more sophisticated mechanisms for getting about. But what did that evolutionary journey look like, and how can we know? We may be able to see fossils of creatures which were present at the time, but there is a big difference between a pile of bones and a moving animal. Now, a team lead by John Nyakatura from Humboldt University in Berlin has used a host of techniques to try and work out how a crocodile-like creature from about 280 million years ago might have moved, in the hopes of better understanding the great transition to land. Noah Baker called him up to find out more.

Interviewer: Noah Baker

Tell me about the animal that you’ve been studying in this particular paper?

Interviewee: John Nyakatura

We have been studying Orobates pabsti from the Lower Permian, about 300 million years old, and it’s a beautifully preserved fossil, complete and articulated. And moreover, there’s fossil trackways which have been assigned to Orobates from the same fossil locality which is very rare.

Interviewer: Noah Baker

What was your approach to work out how this creature might have moved? What was the first step I suppose?

Interviewee: John Nyakatura

We used a highly multidisciplinary approach. First, we were interested in how modern animals use sprawling tetrapod locomotion, so we studied four modern species, extant species, which were quite different in terms of their morphology, or anatomy and also in terms of their ecology and in terms of their position within the tree of life. So, we studied salamanders, the blue-tongued skink, green iguanas, which live in trees actually, and then we studied spectacled caimans, which are much closer to the water. By studying these very different modern animals, we were able to identify general principles of their biomechanics of locomotion, and we assume that if animals today, which are so diverse, have these general principles, that these general principles also applied to the fossil. So, we used this information as a guideline for our simulation study.

Interviewer: Noah Baker

So, you started off by looking at these extant animals and you developed these sort of four key parameters, and then you wanted to look at how the Orobates itself would fit in and to do that you needed to get an understanding of what that skeleton looked like digitally. Tell me what you did there.

Interviewee: John Nyakatura

Yeah, so we used highly precise computer tomography scans to first scan the original fossil, and then derive a digital, three-dimensional skeleton from it.

Interviewer: Noah Baker

And then from that digital skeleton, you can start looking at the way that the bones might have moved, the sort of range of motion of the joints.

Interviewee: John Nyakatura

Right. The range of motion of joints is one thing, but it does not restrict the movements very much. If you just think about, so some people are able to do the splits, right, with their legs, but during normal locomotion they don’t do the splits. So, usually the range of motion in the joints does not constrain the actual locomotion very much, so the trackways are much more helpful in this regard. Therefore, we forced our animated skeleton to move within these trackways, and according to the general principles of sprawling tetrapod locomotion that we observed in the modern animals.

Interviewer: Noah Baker

Okay, so you can animate your digital skeleton to walk inside the trackways – these sort of fossilised footprints – and then you can use the information you’ve learn from extant species to further narrow down various parameters of the walking, like precision or power or balance. But then you still wanted to go one step further, and that’s to prove the kind of theories you’ve come up with from your simulation in the real world. Tell me, what did you do there?

Interviewee: John Nyakatura

Yeah, so simulation is one thing, but to actually prove it in the real world is a different thing. So, the first thing we did is build a robot that actually is able to do all the movements that we also simulated. And of course, there’s friction, there’s gravity, there’s lots of things that act on the locomotion of a physical robot and we wanted to show that the reconstructed gaits that we find likely can be produced by the robot and then we check whether the robot has produced the trackways that we can also find in the fossil record. And by this, we tested our hypothesis a bit about these fossil trackways and the trackmaker.

Interviewer: Noah Baker

Okay, so bringing all of those many different methods together, tell me, did you come up with an answer? How do you think Orobates might have walked?

Interviewee: John Nyakatura

It’s very likely that Orobates already had what we termed ‘advanced locomotion’. So, it was probably lifting its body off the ground quite a bit. It was fairly energy conservative in terms of its locomotion, and in many ways what we found for Orobates resembles what we also found in doing the locomotion of the spectacled caiman.

Interviewer: Noah Baker

And do you know what this sort of more upright gait might mean for Orobates in terms of how it lived?

Interviewee: John Nyakatura

The way to interpret it is not that easy, but it suggests that Orobates probably was quite independent from water. It had a quite effective locomotion on land, and this is something that modern species, we usually don’t see in amphibians.

Host: Benjamin Thompson

That was John Nyakatura speaking with Noah Baker. You can see the Orobates simulation and its robotic counterpart in action in a video on our YouTube channel. Check it out at youtube.com/NatureVideoChannel.

Host: Charlotte Stoddart

Coming up in the show, we’ll be hearing all about a shake-up of science funding in Serbia - that’s in the News Chat. Up next, Anna Nagle is here with this week’s Research Highlights.

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Host: Anna Nagle

New Caledonian crows have a reputation for being very brainy birds, especially when it comes to making tools. But now scientists have shown that these crafty crows can also make smart deductions by observing the world around them. The researchers trained one group of crows to fetch heavy objects and another to fetch light objects, to earn a reward. The scientists then suspended unfamiliar objects in front of a fan, so the birds could see how they responded when buffeted by a breeze. Despite not having a chance to investigate the mystery objects any further, the birds correctly selected the right object – heavy or light – 73% of the time. The research suggests that the crows are able to learn about an object’s properties purely by observing it rather than experiencing it directly. Weigh up that research in Proceedings of the Royal Society B.

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Host: Anna Nagle

A supernova usually marks the death of a star. These enormous explosions are often a single burst that lasts a few months before fading away. But in 2017, astronomers announced the discovery of a rare supernova that continued to shine for more than 600 days. Using data from ground- and space-based telescopes, scientists have now reported that the exploding star’s light finally faded after 1,000 days – around ten times longer than your average supernova. The light from the explosion also trailed off steeply, which doesn’t match most explanations of the star’s strange behaviour. However, the researchers say the signature of sulphur found in the supernova’s light might help narrow down possible explanations. Head over to Astronomy and Astrophysics for more of that illuminating research.

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Host: Charlotte Stoddart

Our next story is about the large proportion of DNA in our bodies that for a long time was considered just junk. But the more scientists understand about so-called ‘junk DNA’, the more functions and purposes they find. Here’s Ali Jennings to tell us more.

Interviewer: Ali Jennings

We carry around in most cells of our body some 3 billion nucleotides – the As, Ts, Gs and Cs that make up our DNA. Some of this DNA codes for genes, but biologists still don’t know what much of the rest of DNA actually does, if it does anything at all. This kind of mysterious non-coding DNA crops up all over our genome. It can even be found scattered within genes, breaking up their coding sequence. These stretches of gene-interrupting, non-coding DNA are called introns. When a gene is required, its DNA is transcribed into RNA, which contains these non-coding introns. In most cases, the introns then have to be cut out, after which the coding RNA is stuck back together. This process is called splicing. After they’ve been spliced out, the introns have no function and are left to degrade – or so we thought. Here’s David Bartel from the Massachusetts Institute of Technology in the US. David and his team examined introns in single-celled yeast by sequencing their RNA.

Interviewer: David Bartel

So, what we found was that whereas many of the introns in yeast are rapidly degraded, there are some conditions in which these introns stick around, and are stabilised.

Interviewer: Ali Jennings

But these stabilised introns weren’t sticking around all the time.

Interviewer: David Bartel

These introns that were accumulating were not accumulating, you know, when the cells were happily growing and doubling every few hours. They would only accumulate when cells were under long-term stress.

Interviewer: Ali Jennings

David and his team set about finding out why introns accumulated when the yeast cells were under stressful conditions. But meanwhile, another team from the University of Sherbrooke in Canada were also discovering that introns were playing a role in yeast cell survival. Here’s Sherif Abou Elela, who led the second group’s research.

Interviewee: Sherif Abou Elela

So, we deleted every one of the 290-odd-so introns in yeast, and then start looking at their effects one by one. So basically, what we have found is in normal conditions, introns are not required, but when we delete them we are having a major effect when nutrients are depleted or when the cell starts to starve.

Interviewer: Ali Jennings

Independently, Sherif’s and David’s teams had both discovered that introns are important for yeast survival under testing conditions. And David thinks he knows why.

Interviewer: David Bartel

So, the introns, they’re not just stabilised alone in the cell, just floating around as a naked RNA. Instead, they’re part of a complex, and this complex contains some of the machinery that was used to splice the introns out of RNA. These stable introns are sort of tying up some of the splicing machinery, preventing that machinery from working on other RNA and in doing so, that is helping to slow down the growth of the cells.

Interviewer: Ali Jennings

When nutrients are limited, slowing down growth helps yeast cells to save precious resources, increasing their chances of survival. Both David and Sherif think introns allow a cell to do this by tying up their splicing machinery. This limits the resources spent on production of mature RNA and protein. But whereas David thinks that this happens after the introns have been cut out, Sherif thinks that introns impact splicing whilst they’re still part of the initially transcribed RNA. Such previously unreported functions of introns would be big news in the world of biology, but both Sherif’s and David’s studies have worked in yeast cells. Could this process be happening in human cells too? David’s not sure, but Sherif is optimistic.

Interviewee: Sherif Abou Elela

So, the kind of the elements, the players if you like, for this mechanism do exist, so we expect the essence of what we discovered will also happen in humans. What is really to be seen is whether or not the splicing equilibrium in a very complex organism would actually be as sensitive to a change or a deletion of a single intron.

Interviewer: David Bartel

I think that if there is a lot of this happening in human cells, that it would have been seen, and so if there is some use for stable introns in human cells, then it’s probably happening in conditions that are very unusual that haven’t been looked at carefully yet.

Interviewer: Ali Jennings

In these two papers, published back-to-back in this issue of Nature, Sherif’s and David’s team have reported a new role for introns in yeast cell survival. But it remains to be seen if this mechanism is found in other organisms, and if so, whether it plays an important role.

Host: Charlotte Stoddart

That was Ali Jennings talking to David Bartel and Sherif Abou Elela. You can read both of their papers over at nature.com/nature, and you can see a video all about introns, featuring old-fashioned cassette tapes, over at youtube.com/NatureVideoChannel. Intrigued? Go and check it out.

Interviewer: Benjamin Thompson

Finally then, it’s time for the News Chat and making his debut is Mićo Tatalović, news editor here at Nature. Mićo, hi!

Interviewee: Mićo Tatalović

Hello.

Interviewer: Benjamin Thompson

We’re going to head to Serbia today for our first story, and we’re going to talk about research funding. Now, maybe for those people who don’t know about the sort of state of research funding in Serbia could you maybe explain it a little bit?

Interviewee: Mićo Tatalović

Yeah, sure. So, Serbia is a small country in eastern Europe. It’s not especially rich, so they don’t have a huge amount of funding for research. I think the government funding is in the range of €100 million a year. One of the biggest problems for researchers there is that the government hasn’t launched a call for research grants in almost ten years.

Interviewer: Benjamin Thompson

Ten years? I mean, here in the UK we imagine sort of you’d apply for a grant every three of four years. Why the difference there?

Interviewee: Mićo Tatalović

Yeah, so I think that was the idea there as well, but what happened was that last time they tried launching a grant call which was 2016, researchers complained because they kind of felt that there wasn’t enough money for research, and also there was a snap government election and science was kind of, I guess, set aside and they never came back to making those calls. So in effect, most scientists in Serbia have been working with the same research proposals that they drafted like ten years ago, and obviously science has moved on since.

Interviewer: Benjamin Thompson

Well quite, and I’m sure new fields of science exist now that maybe didn’t a few years ago. But are things about to change, Mićo, and how so?

Interviewee: Mićo Tatalović

Yeah, so the government is proposing several or a couple of laws on science. One of them has already been passed in the parliament and the idea is to set up a national research fund and hopefully the expectation is that this fund will then launch the first calls in ten years, so scientists are waiting for this call, but awaiting it with mixed feelings because they don’t know the details and they don’t know how much money will be in the new fund.

Interviewer: Benjamin Thompson

I mean, big question I suppose for me here is where is this money going to come from?

Interviewee: Mićo Tatalović

So, the government says they’re going to increase funding themselves and they have some funding from the World Bank and from the EU, so Serbia is one of the countries that wants to get into the European Union and the EU has funds for supporting things like science in those countries. But in the long run, the Serbian government wants a lot of the funding to come from the private sector.

Interviewer: Benjamin Thompson

I mean you say maybe mixed feelings among researchers in the country, I mean more money seems like a good news story. Why the discrepancy there?

Interviewee: Mićo Tatalović

Part of the reason is that scientists just don’t seem to believe the government, so they say we’ve heard these promises before, right, so they’re kind of really waiting to see whether these promises come true before they can kind of really trust the government. And even the science minister admits that this is true, they are kind of aware and they say that they are hoping to rebuild that trust, so we’ll see if that happens or not.

Interviewer: Benjamin Thompson

And how long will the researchers have to wait to find out then?

Interviewee: Mićo Tatalović

So, I think they’re expecting these new calls for research grant sometime in mid-to-late 2019, so another few months at least. And what will happen in the meantime is that the government will be passing another law which will regulate how salaries are paid out. So until now in Serbia, a lot of scientists had to have a research grant in order to get a salary because they would get salary out of their grant, and the idea now is that they won’t have to do that, so they’ll get salary automatically. So that could be good news for some but not for all of them, and some people are saying that some researchers who work at the university faculties will be affected negatively by this law because for them, it won’t mean an automatic salary, it will mean no salary at all. So, they might actually lose their jobs and they might have to find different jobs.

Interviewer: Benjamin Thompson

Okay, right, so potentially, you know, fairly wholesale changes. Is this going to be evaluated in sort of in the medium term to see how well it’s worked?

Interviewee: Mićo Tatalović

There’s no sense at the moment that it will be evaluated. What the government is doing, they’re kind of putting these proposals to the public debate and they’re saying that they’re listening to what the community is telling them so hopefully they will incorporate some of these changes to improve things, but it’s not clear whether and how this will work and whether they will evaluate it or not.

Interviewer: Benjamin Thompson

Well, let’s move on to our second story, Mićo, and this is about crowdfunding – getting people online to donate money to a particular project. Now, I’ve crowdfunded a few projects myself – rereleased LPs of video game soundtracks – so I’m aware of the process, but I didn’t know that this was a method being used to fund science.

Interviewee: Mićo Tatalović

Oh yeah, definitely, so there’s several sites that facilitate this, so they allow scientists to come to these websites, explain their projects and get some money. And one of the biggest such websites is something called Experiment.com, which is based in the US, and they have something like over 1,000 active projects there as we speak, and scientists are getting some money that way. It’s not huge amounts of money but, you know, it’s in the range of a few thousand dollars.

Interviewer: Benjamin Thompson

Well, do we know what sort of researchers are using these systems to get this funding?

Interviewee: Mićo Tatalović

So, you know, there’s a new study that looked into that – who gets the funding and how much they get – and you would maybe expect that, you know, more senior scientists and professors would get most funding, but actually they found that students are getting more money that more senior scientists. Another interesting thing is that, you know, traditionally when you’re applying for a funding grant, you would want to list your research publications to show that you’re a good scientist, but here they found that it didn’t matter whether you listed your publications or not.

Interviewer: Benjamin Thompson

Oh right, so maybe then this is a bit more of a sort of popularity contest. Is this because people are putting forward proposals that tend to grab people’s attentions and, dare I say it, are young people more used to kind of social media and internetting than more senior scientists?

Interviewee: Mićo Tatalović

Possibly, yeah. I mean the study finds that crowdfunding research flips science’s traditional reward model, so it’s not the people you would expect to get the funding that get the funding, but the study didn’t really kind of analyse or find why this is so, right. So, the researchers say it could be that maybe younger scientists are just more savvy on social media, but they haven’t really looked into that so they can’t know for sure why it’s happening.

Interviewer: Benjamin Thompson

One thing that gets me about this, Mićo, is the system as a whole. So, I’ve mentioned that I’ve done some sort of crowdfunding projects, and I got a tangible thing at the end. With scientists, this is kind of different, right? It can be years before you see a result, if you see a result at all. Have the people behind this study looked at that?

Interviewee: Mićo Tatalović

So, they haven’t analysed that yet. Some of these proposals definitely do get funded. In our story, we mentioned one scientist who has done a crowdfunding campaign before in 2012, and he actually managed to get some like $350,000 through this with his team, and they launched this whole project. They even had a spin-off company later on from that, so some scientists are having real-world effects with these crowdfunding projects. What some of the scientists are saying though is that the real interest in crowdfunding is that basically they’re free. There’s no bureaucracy that comes with traditional research funds.

Interviewer: Benjamin Thompson

Well, Mićo, thank you so much for joining us. Listeners, as always, head over to nature.com/news to read even more about these stories.

Host: Charlotte Stoddart

That’s it for this week’s show, but we’ve got a few things to highlight before we go.

Host Benjamin Thompson

Yeah, that’s right. If you’re a fan of science podcasts – and I sincerely hope that you are – then we’ve an article in our Careers section about making your own. Head over to nature.com/careers to have a read of that.

Host: Charlotte Stoddart

And don’t forget to give those videos about the fossil robot and the junk DNA stories a watch. They’re on our YouTube channel where you’ll also find one about how to help pollinating insects in our cities. I’m Charlotte Stoddart.

Host Benjamin Thompson

And I’m Benjamin Thompson. See you all next time.