周期蝉爆发，浣熊异常活跃？常温运输蛋白质的凝胶；家庭堆肥可分解的塑料 | Nature Podcast

本期Nature Podcast为您带来，新型凝胶可以安全运输蛋白质、蝉的大量繁殖让浣熊活跃起来、葡萄收成揭示欧洲600年来的气候变化、工程酶助力制造可降解塑料、如何让实验室培育的肉吃起来更有肉味、月球地下洞穴：或许是未来人类栖息地，欢迎收听本期内容！

2021年，印第安纳州的浣熊在蝉爆发期间异常活跃。图片来源：Bertie Gregory/Nature Picture Library

一名工人正在收获酿酒的葡萄，而葡萄的甜度取决于果实成熟时的温度和日照水平。图片来源：Sameer Al-Doumy/AFP/Getty

使用风味可切换支架培养的肉类。图片来自延世大学。

静海坑（月球上已知最深的坑）的雷达影像表明，它是一个地下洞穴的入口。图片来源：NASA/GSFC/Arizona State University

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Benjamin Thompson

Welcome back to the Nature Podcast, this week: a protective gel that lets you post proteins…

Emily Bates

…and a plastic that you can compost at home. I’m Emily Bates.

Benjamin Thompson

And I’m Benjamin Thompson.

First up then this week, I just wanted to introduce Emily Bates. You may have heard her reading the Research Highlights last week, but now Emily is here to host the show for the first time. Emily, hi.

Emily Bates

Hello, Ben, how you doing?

Benjamin Thompson

I am doing A-OK. It's great to have you with us in the hosting chair for the first time.

Emily Bates

Absolutely fantastic to be here, looking forward to it.

Benjamin Thompson

Excellent. Well, let's start with our first story this week, which seems like the right place to do so. And we’re all used to the idea of reaching into the fridge when we want milk for our tea, or opening the freezer when we want some peas for our dinner. Now, these technologies help us store food for longer, so it’s still fresh when we want it — and the same thing applies to many of our modern medicines. Protein-based therapeutics like insulin or antibodies used to treat cancer, are often frozen or freeze dried to keep them in optimum condition for when they reach their destination. But while these methods are effective, they can be expensive, time consuming and not conducive to low-resource settings. But, this week in Nature, researchers are presenting an alternative way to get these vital proteins where they need to go. A gel that can store them that is quick, simple and cheap. Reporter Anand Jagatia spoke to one of the paper’s authors, Matthew Gibson, about the research, and started by asking him to explain what goes wrong with proteins if they aren’t stored properly…

Matthew Gibson

Protein isn't alive. It's essentially a big macromolecule piece of spaghetti, if you like, that folds itself into a structure that then gives the function which we all know, proteins can perform. So really it was about, how do you stop them from unfolding, but in particular, how do you stop them from aggregating? So one protein on its own will normally function, but when they start to stick together with themselves, you find that they lose a bit of their activity, or they become insoluble and this is made worse by shaking them. So, one of the most famous examples of this is in insulin. When you prepare it, if you shake it vigorously, that actually promotes this aggregation.

Anand Jagatia

I think people will probably remember from the pandemic that there was a lot of talk about cold-chain technology or cold-chain management, and that it's not enough to create a vaccine, or could be a protein or an antibody or whatever, you have to be able to store it and transport it. And so we do have ways of doing that, but it's– it's difficult, isn't it?

Matthew Gibson

Yeah, so the cold chain works really well. You know the example in COVID was the mRNA vaccines, for example. So not protein, so bit of an aside from what we've done. One of the things when they first emerged was how everyone had planned for them to be delivered in minus-80 degrees C freezers. So these use an awful lot of energy. So your one minus-80 degrees C freezer can use as much as, say, someone who's living in a small house on their own.

Anand Jagatia

So freezing proteins comes with considerable energy costs. Are there any other downsides to the way that we currently store proteins and other molecules?

Matthew Gibson

Yeah, so the freeze-thaw process itself is pretty strenuous. Once frozen, things store well but getting down to temperature and getting up to temperature is where an awful lot of the damage can occur. On some proteins if you freeze-thaw them, you do get some aggregation. But really, the other really good way storing proteins is freeze drying. So a bit like we freeze-dried coffee, we remove all the water, and then you've got a nice, stable, solid powder. It’s a solid protein, and that's not what goes into someone. So you've got to crack open the liquid, get that into the solid, and you've got to dissolve it, and you've got to follow those instructions. So this is where we're wondering, what other technologies can we bring to it, which are as universally useful as some of the freeze-drying and freezing methods, but are really, really simple, but have the benefit where the user doesn't have to decide how concentrated it would be by mixing different components together.

Anand Jagatia

What was your approach, then? How did you decide to tackle this problem?

Matthew Gibson

So, the way we tackled this was with our collaborators at Glasgow University. Professor David Adams he's really an expert on making gelator molecules. So what we mean by this gelators are small molecules, when you put them in the right conditions, they sort of stick together and they form these big networks. And that stops the movement, and it becomes a gel, a bit like a jelly. So by slowing down the molecular motions within the gel, the proteins won't come across each other and then we can switch off the aggregation.

Anand Jagatia

So if I sort of try and scale this up by analogy, to like human level. If me and you were sort of floating around in a big, like swimming pool of jelly or gel, it would be quite difficult for us to move through it and to reach each other, and so we'd kind of just be stuck separate. Is that kind of what's happening with the gel and the proteins?

Matthew Gibson

Exactly. So if we're in a normal swimming pool, if we just swam at random we're going to run into each other eventually. If you and I try and swim in some jelly, it would take us a while to run into each other, and the frequency of that would be significantly decreased. But of course, then we've got the problem we're going to want to get out of the swimming pool at some point.

Anand Jagatia

So how do you get the proteins out of the gel, then? How did you solve the second issue?

Matthew Gibson

These gels, they have a unique property, and then we say they're quite stiff. They're almost a bit brittle. When we push the gel out of the syringe with a small filter on the end, we sort of shatter the internal network of the gel. And as you push, none of the gel came out of the syringe, so all we got was pure protein in the salts and buffer.

Anand Jagatia

So how did you actually go about testing the performance of these storage gels and how well did they do at protecting the proteins?

Matthew Gibson

We took an enzyme, it's called β-Galactosidase. We actually showed that if we even heat it up to 50 degrees C, we retain some of that protein function. And we also stored some insulin. We showed that when it's in our gel, if you shake it at 600 rpm, insulin that comes out is not aggregated. The experiment we were most proud of was we put a temperature tracker in with one of our gels and we thought we'd subject it to a random test. So we just used the post. So we put these things in the post and sent them back to ourselves to collect them. We could see it's been through quite a range of temperatures. It's probably been dropped, right? It got dropped into a post box, and the protein we recovered was perfect. So that was the thing which made us most confident this worked.

Anand Jagatia

Now you've done the proof of concept. What's next for your lab in terms of getting these gels tweaked and finalised and potentially out into the real world?

Matthew Gibson

We can change the structure of the gels a lot, so we are looking a little bit to really make sure we're on the optimum gel and that we can use this and as many different types of protein as possible. So that's the first thing, which we're really having to check. Also, long term so how far can we go? Is this for something that you might want to bank for six months, or is it three or four years?

Anand Jagatia

And one of the potential areas where this could be really impactful is in low-resource settings. You know, countries that where they don't really have reliable electricity, there's no way they're going to be able to keep a minus 80 degree fridge running constantly and often they're the places where you need to send some of these therapeutic molecules.

Matthew Gibson

This is really where we want to be looking at. So are there protein vaccines which would respond really well in our scenario? So they can be all dosed and metered at production, and then when they're sent to their final location, you don't need the high electricity storage conditions, we also don't have the worry of transient warming events, and those combinations is where we really think for these low-resource environments for both human and maybe animal health as well.

Benjamin Thompson

That was Matthew Gibson from the University of Manchester here in the UK. For more on that story, check out the show notes for some links.

Emily Bates

Coming up, how embedded enzymes could make plastic more biodegradable. Right now, though, it’s time for the Research Highlights, with Dan Fox.

Dan Fox

In 2021, a huge cicada emergence had an unexpected knock-on effect — extra raccoon activity. Cicadas are insects that spend most of their lives underground, only to emerge en-masse at the end of their life cycle to reproduce. One of the largest emergence events in recent history occurred in 2021, when three cicada species on a 17-year cycle emerged in the space of just two months in the eastern United States. A team of researchers wanted to know what effect this emergence might have on the local mammal populations and set up camera traps and audio recording devices across two areas of Indiana. The team looked at eight species and found most of them carried on as usual during the cicada invasion, but raccoons became more active during the event, possibly so they could feast on the readily available insects. Meanwhile, white-tailed deer appeared less frequently, perhaps avoiding areas where the hum of insects could make it harder to hear predators. You don't need a camera trap to catch that research, it's in the Journal of Mammalogy.

Records of the quality of annual wine-grape harvests can be used to estimate historical summertime temperatures across western Europe. Weather and harvest quality are interlinked: grape vines like their summers hot and sunny, and their favourite weather leads to production of grapes with high sugar levels. A team of researchers analysed records of the sugar content of wine must — the mashed grape juice before it's fermented — in western Europe from 1420 to 2019. Combining this analysis with climate records to build a model that estimates harvest quality summertime temperature and precipitation at locations where the wine was produced. Their analysis shows that the quality of grape harvests oscillated for more than 500 years before increasing sharply in the latter part of the twentieth century, as human-induced global warming resulted in longer and hotter summers — and better wine grapes. You can pick up that vintage research in Climates of the Past.

Emily Bates

Next up on the show, reporter Nick Petrić Howe has been finding out about a new plastic that can biodegrade in a home compost heap.

Nick Petrić Howe

I probably don’t have to tell you that plastic waste is a huge problem, with millions of tonnes of the stuff being produced and thrown away every year. What’s more, plastic often lingers in the environment for hundreds of years. To avoid a continued build-up of plastic rubbish, manufacturers have been increasingly turning to polylactide or PLA, a plastic derived from plant material that should completely break down over time. But only under certain conditions.

Alain Marty

It is considered as biodegradable at high temperature. And high temperature means higher than 60 degrees.

Nick Petrić Howe

This is Alain Marty, the chief scientific officer at the biochemistry company Carbios, who has been working to find a way to get PLA to biodegrade at lower temperatures. And this would be useful, because currently this plastic can only be broken down in special industrial facilities, and PLA can’t just be chucked onto someone’s compost heap, as these don’t get above 60 degrees. Alain and his colleagues have been investigating if enzymes could help break down PLA more efficiently. These little proteins have shown promise at breaking down plastics, and the team wondered if embedding an enzyme into PLA could reduce the temperature where it breaks down. There is evidence that this works for other plastics, but while straightforward on paper, for PLA the reality was somewhat different.

Alain Marty

When the CEO of Carbios 12 years ago proposed me this challenge. My first question was, ‘how to introduce an enzyme in a plastic?’ because I was not familiar with plastic industry. And the answer was, we will melt the polymer, and we will introduce this enzyme. And my second question was, ‘what is the melting temperature of PLA?’ and the answer is 170 degrees Celsius. And I said, I think it will not be possible.

Nick Petrić Howe

But Alain wasn’t going to be defeated that easily. Previous studies have found enzymes that can break down PLA, but these wouldn’t be able to withstand the high temperatures in the plastic production process. So, the team set about looking for an enzyme that could. They started with a known PLA-eating enzyme that is found in a bacterial species. And then they isolated it and tried to figure out how to make it work a bit better, as Isabelle Andre, part of the team from the University of Toulouse, explains.

Isabelle Andre

And we started to engineer this enzyme so that’s where actually we used molecular modelling to understand how the PLA could be recognised by the enzyme and identify some residues that could be key and that actually could be mutated to improve the activity of the enzyme.

Nick Petrić Howe

The team were able to find the key amino acids in the enzyme that they could change to improve how well it works. They then used this knowledge to make a beefed-up version of the enzyme, which was great at breaking down PLA. Sadly though, it still couldn’t survive the high temperatures that it would encounter during the plastic production process.

Isabelle Andre

So that's when actually we decided to also search for homologs in the natural biodiversity. So we used bioinformatics tools to identify some enzymes, and we came up with an enzyme that was less efficient, but that that actually showed the higher thermal-stability.

Nick Petrić Howe

So now the team had two similar enzymes: one that could break down PLA a bit, but survive at higher temperatures, and one that couldn’t but was very good at breaking down PLA. The next step was to combine them, to create a new enzyme that could do both. The team did exactly this and ended up with an enzyme that could break down PLA well and withstand the high temperatures but then they were faced with a different problem. How do they get it into the plastic? Enzymes have been embedded in plastics before, but previous attempts have used enzymes in powdered form, which limits how thin the final plastic can be — making it difficult to use for things like shopping bags or food packaging. To get around this, the team introduced the enzyme into the plastic moulding process as part of a liquid formulation. This had a dual benefit: it mixed better in the melted plastic, and further protected the enzyme from heat. With all that in place, the next question was how well the enzyme infused PLA broke down.

Alain Marty

What we proved is that, first of all, this plastic is only biodegradable in presence of water. It means that during the storage there is no biodegradation at all. And then it is just when the plastic ends up in a compost, we demonstrate is that the total biodegradation is realised in less than 26 weeks.

Nick Petrić Howe

When in warm, wet conditions, like a home compost bin, the plastic will break down about 26 weeks. A big improvement over just regular PLA which would still need a long time in special industrial conditions to break down. Ting Xu, a material scientist who’s also worked on enzymes to break down plastics, was impressed by the research.

Ting Xu

The work is definitely, it’s very important and has a lot of relevance for years to come.

Nick Petrić Howe

Ting believes that being able to program when a plastic is broken down is going to be important to deal with plastic waste, and by embedding an enzyme, like the team did here, you can achieve that, and in a more efficient manner by having dedicated enzymes to break down the plastic.

Ting Xu

First of all, you really make the enzyme to be accessible to the plastic that is buried deep down, instead of just having a surface erosion. And the other thing is that you have a lot of enzymes working at the same time for you, instead of just relying on whatever the environment have at the time, that's a really, you know, large variable. But by putting the enzyme inside of the plastic, you know where they are.

Nick Petrić Howe

The one caveat Ting did have though, was that with this being an engineered enzyme, rather than a naturally occurring one, she’d like to know what would happen to it long term.

Ting Xu

So if they leach out into the environment, what is going to be their impact for the long term? Personally, I think they should be pretty safe, because enzyme is not particularly stable; nature may have different ways to deactivate, but that's the part that, you know, I think the community probably should spend some effort to investigate.

Nick Petrić Howe

Alain and the team say that the enzyme will degrade in the environment and recently they’ve gained authorisation for the product to be used in the United States — which means that it’s had to go through various checks to make sure that the enzyme is safe to use and doesn’t transfer to food. In fact, come 2025 we may start to see this kind of enzyme-embedded PLA plastic available, which Alain thinks will really start to change how plastic waste accumulates.

Alain Marty

For single-use plastic I think this work is a revolution, because it will enable to replace, for instance, polyethylene packaging. And you cannot imagine biodegradation with polyethylene. Then the challenge is to replace polyethylene by PLA but this innovation offers a way to make a packaging fully biodegradable.

Emily Bates

That was Alain Marty, from Carbios, in France. You also heard from Isabelle André, from the University of Toulouse, also in France, and Ting Xu from the University of California, Berkeley, in the US. For more on this story, check out the show notes for some links.

Benjamin Thompson

Finally on the show, it’s time for the Briefing Chat, where we discuss a couple of articles from the Nature Briefing. Emily, why don’t you go first this week? What have you been reading this week?

Emily Bates

I've got a story I read about in Nature, and it's based on a Nature Communications paper all about making lab-grown meat actually taste, well, like meat.

Benjamin Thompson

All right, so lab-grown meat then, so this isn't fake meat, but it's also not real meat. How are we defining lab-grown meat here?

Emily Bates

Yeah. So it's cultured meat. It's produced by growing animal-cells in the lab. So normally, they take stem cells and turn them into muscle cell and that's what they use to create these, what we call lab-grown meats. Some people believe that this is the future of meat. There's no need to slaughter an animal, and it could, in the future, have a lower carbon-footprint than rearing livestock does, if we can get the technology right.

Benjamin Thompson

And one of the things to overcome then is to make this lab-grown meat taste meatier. Is that right?

Emily Bates

So they've really focused on the texture and making it look like meat. So you get things like steak and meatballs, but matching the taste has always been quite challenging. The traditional meat flavours are very complex and they don't do particularly well in a lab setting.

Benjamin Thompson

Well, researchers are getting towards getting the look down then, but I guess a lot of eating is in the smell and the taste, and this has been hard to recreate the real deal then.

Emily Bates

Yeah, so when conventional meat is cooked at high temperatures, it undergoes something called the Maillard reaction and this is when amino acids and sugars react with each other, and it's what gives the meat that recognizable aroma and taste, and also that kind of golden-brown colour that you get. You know, the crispy bits that make you go, oh, that looks quite nice actually. So what the researchers have done is they've developed a compound that contains a product of the Maillard reaction that is known to contribute towards the sort of savory profile of meat, and they made it what they call switchable, meaning that the flavor would only be released when the meat was heated to around 150 degrees C.

Benjamin Thompson

So there's kind of a mirror there too then. So almost the process of heating, of cooking, releases what it's supposed to taste or smell like. Is that right?

Emily Bates

Yeah. So they tested it by using what's called an electronic nose, which is a device that analyses the chemical makeup of smells, and they found when they heated this lab-grown meat, it produced compounds that were associated with savory, fruity and meaty flavors. But it wasn't until it's heated up, so before then the nose was like, this is just some weird gel. Which is another thing we should probably talk about. They added this compound that they created to a hydrogel, which is a sort of jelly-like material that's used as the scaffold for the stem cells that they grow into muscle tissue.

Benjamin Thompson

Right.

Emily Bates

It's what allows the sort of meat to begin but it means that it's not the most appetizing looking thing in this situation. It kind of looks like a translucent pink gel-disc. It doesn't scream of a hamburger or a steak or anything like that.

Benjamin Thompson

Mmm mmm, so it seems then there's one strand which is getting it to look right and there's another which is getting it to taste right. Is it going to be straightforward to kind of combine the two things together?

Emily Bates

Well, there's a slight issue with this study in that the materials and the culture medium that they used have not been approved as edible. So this meat isn't going to be used to nourish humans. It's not going to be the be-all and end-all, but it's just a proof of concept, and maybe in the future, they'll be able to make it edible.

Benjamin Thompson

Well, that does seem like a fairly important bridge to cross, then, in terms of getting this lab-grown meat to look and smell like the real thing, as we say there. But let's move on to my story this week, Emily, and it's a story that I read about in The Guardian, and it's based on a paper in Nature Astronomy, and it's about an underground cave on the Moon. I think this has got a few people quite excited.

Emily Bates

I wasn't aware that there were caves on the Moon.

Benjamin Thompson

Well, that's totally reasonable, I think. And for a long time, researchers, you know, speculated that there was caves and tunnels under the lunar surface. It was thought then that this underground system was formed by lava flow, right, making these things called lava tubes, but there was no real direct proof, right. It was kind of hard to come by. Now, there have been a bunch of images of pits on the surface of the Moon, right, at different elevations and different locations, several hundred of them, from what I understand. And it was kind of speculated that these were collapses of this underground network. But as I say, this has been kind of inconclusive, but that's where this paper comes in and maybe kind of tipped the balance the other way, a little bit.

Emily Bates

Interesting. And so how did they actually discover this one? What was the process?

Benjamin Thompson

Well, in 2010 actually, this pit was detected by NASA's Lunar Reconnaissance Orbiter. Okay. And what the team here have done is they've actually gone back and reanalysed some of the data from this mission, obviously several years later, and using new techniques. And what they've discovered is that there were some radar reflections from inside this pit, and they put forward that the likely explanation for this is that there is an underground cave. Now, it seems like quite a substantial sized thing, right. And it's accessible from this pit, which is in this area of the Moon called the Mare Tranquillitatis, okay, the Sea of Tranquillity–

Emily Bates

–ah–

Benjamin Thompson

–which is, of course, where the Apollo astronauts first set foot on the Moon–

Emily Bates

–right–

Benjamin Thompson

–and this is an ancient lava plain. And it turns out then that this cave, if that's what it is, is 150 meters below the surface, maybe 45 meters wide, and potentially up to 80 meters long. And in this article, they say that's about the size of 14 tennis courts, so a pretty big space.

Emily Bates

So is this the kind of thing that we might be looking to set a base up on? Or is that fanciful?

Benjamin Thompson

Potentially fanciful, but it's what a lot of people have been speculating for a lot of time. But before we get into that, let me do the sensible thing. Right now I think researchers are super interested because the rocks inside this cave will probably be an absolute goldmine, if you'll pardon the pun, for the history of the Moon and the volcanic activity there. But you're right, it seems that the way the wind is blowing is that humans want to set up bases on the moon. Now, the moon is a pretty inhospitable place–

Emily Bates

–right–

Benjamin Thompson

–we covered it on a book podcast not so long ago, so I'll put a link to that in the show notes. And there are these absolutely huge temperature swings. It's absolutely battered by radiation, and the threat of meteorite strikes is kind of ever present. So these geodesic domes on the surface that we were promised in the 1960s seem very, very unlikely, but if you could live underground that could mitigate a lot of these issues, right? Much more stable temperature, more protection from impacts and radiation. So that's what's been put forward. But it's always been tough to actually prove that these things are there and find one, and that's what they've done in this instance.

Emily Bates

This almost feels too good to be true.

Benjamin Thompson

I mean, yes, that's fair. I think there are a bunch of issues here, right? And of course, the first one is: researchers have got absolutely no idea what this underground cave looks like. You know, jagged rocks abound, so having a cave that's full of those will make it more difficult to potentially live there and also to get into it is a drop of over 100 meters.

Emily Bates

Oh, okay.

Benjamin Thompson

And a bunch of steep slopes that, uh, yeah, could potentially make avalanches happen for the people at the bottom. So it might be fanciful that this is the one. But of course, while this is n=1, it does show that potential collapses of these tubes that form entrances to this underground world do exist.

Emily Bates

Yeah.

Benjamin Thompson

And so, I think researchers will be going back and looking a lot harder at previous data and looking for other evidence of this. But you know, as we've said there, you know, it seems like lunar exploration is huge business right now for private companies and for various governments and nations around the world. So, finding somewhere that folk could stay relatively safe, I think relatively is an important word to use there, would be a real boon for these missions moving forwards.

Emily Bates

So, no holidays to the Moon just yet, but maybe in the future, some research going on underneath the surface.

Benjamin Thompson

Yes. I mean, that seems like a reasonable thing to say and also a reasonable place to end this Briefing Chat. Thank you, Emily for making it your debut this week. And listeners for more on those stories and for where you can sign up to get more like them direct to your inbox, check out the show notes for some links.

Emily Bates

And that’s all for this week. As always you can keep in touch with us on X, we’re @NaturePodcast, or you can send an email to [email protected]. I’m Emily Bates.

Benjamin Thompson

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

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