NATURE PODCAST

Why skin grows bigger as you stretch it

Skin's unusual response to stretching is finally explained, and the latest in a huge effort to map DNA.

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Listen to the latest from the world of science, brought to you by Nick Howe and Shamini Bundell.

In this episode:

01:06 Stretching skin

For decades it’s been known that stretching skin causes more skin to grow, but the reasons why have been a mystery. Now, researchers have uncovered a mechanism to explain the phenomenon. Research Article: Aragona et al.; News and Views: Stretch exercises for stem cells expand the skin

07:49 Coronapod

We discuss how the coronavirus pandemic has affected scientific meetings and how the learned societies that organise them are adapting. How scientific conferences will survive the coronavirus shock; How scientific societies are weathering the pandemic’s financial storm; A year without conferences? How the coronavirus pandemic could change research

18:18 Research Highlights

A genetic trait for pain-resistance, and the accessibility-aware ancient Greeks. Research Highlight: A gene helps women in labour to skip the painkillers; Research Highlight: This temple was equipped with accessibility ramps more than 2,000 years ago

20:42 ENCODE updates

The ENCODE project aims to identify all the regions in the human genome involved in gene regulation. This week, data from its third iteration has been published and we examine the highlights. Research Article: Snyder; News and Views: Expanded ENCODE delivers invaluable genomic encyclopaedia

28:50 Briefing Chat

We take a look at some highlights from the Nature Briefing. This time we look at how smallpox may be much older than previously thought, and how the Earth’s atmosphere rings like a bell. Nature News: Smallpox and other viruses plagued humans much earlier than suspected; Physics World: Earth’s atmosphere rings like a giant bell, say researchers

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Transcript

Listen to the latest from the world of science, brought to you by Nick Howe and Shamini Bundell.

Host: Nick Howe

Welcome back to the Nature Podcast. This week, how stretching skin leads to more skin…

Host: Shamini Bundell

And the latest in DNA mapping news. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe.

[Jingle]

Host: Nick Howe

As you may be aware, our spin-off podcast Coronapod is now part of this show, so if you just want to hear the latest coronavirus updates, check out the show notes for all the timings so you can skip ahead and listen to that. Although, there’s plenty of great non-corona science if you stick around. So, what have we got first on the show this week, Shamini?

Host: Shamini Bundell

Well, reporter Benjamin Thompson has been looking into skin, and I’ve been trying to find a way to explain this without sounding like a serial killer who wants to steal your face, but the skin is a genuinely remarkable organ. Every day it’s subjected to constant stretching, folding, compressing, yet it manages to maintain its integrity, keeping the outside out and the inside in. One peculiar property that the skin has is that if you do stretch it, it responds to the stretching by growing more skin. Now, quite why this is the case has been unclear, but that might be about to change. This week, a paper in Nature outlines the mechanisms underlying this property. Benjamin spoke to one of the authors of the paper, Cedric Blanpain from the Université Libre de Bruxelles in Belgium, who explained how the structure of skin makes it so good at what it does.

Interviewee: Cedric Blanpain

The skin is our first barrier against the external environment and so for that, the skin needs to be always in a perfect shape, and so the skin is renewing itself through the life of the animals. And so, the structure of the skin is organised in a way that the stem cells will divide and produce progenitors, which in turn will generate several layers of cells that really seal the skin from the external environment.

Interviewer: Benjamin Thompson

One of the things then that skin is quite clever at is that if you stretch it, you get more of it, and this characteristic is something that’s been taken advantage of in the reconstructive surgery world.

Interviewee: Cedric Blanpain

Plastic surgeons are using this technique, for example, to cover a big burn or a big scar. It’s also very, very frequently used after mastectomies, so the removal of the breast for breast cancer. Plastic surgeons reconstruct the volume of the breast by putting a skin expander underneath the skin and then they inflate this prosthesis, and this will generate the excess of skin. That’s something very important for the patients that are treated. But the mechanisms that were underlying this stretching in new skin expansion was very not known.

Interviewer: Benjamin Thompson

And this is where your new paper comes in then. You’ve been looking at the mechanisms, and you’ve made a mouse model that sort of mimics what happens during human reconstructive surgery. What did you do, specifically?

Interviewee: Cedric Blanpain

So, for that, we put a little piece of hydrogel under the skin of a mouse that, from hydration with the water of the body, inflates and induces this skin expansion, and with that we could measure the activity of the stem cells and their progeny. We could interrogate which are the genes that are changing every single cell around this skin expander.

Interviewer: Benjamin Thompson

You mentioned stem cells there then, and it seems like these cells at the base of the skin are very sensitive to mechanical stretching. What happens to them when the skin is being stretched when the hydrogel is expanding?

Interviewee: Cedric Blanpain

The stem cells make adhesions with their neighbours and upon stretching, these adhesions are stretched themselves, and that’s probably the initiation of the response. And so, when these adhesions are remodelled, first, the cytoskeleton, which is the skeleton of the cells, reacts to this stretching and they’re actively signalling pathways and gene activation responsible for the stem cells to divide and to differentiate and to generate this excess of skin.

Interviewer: Benjamin Thompson

So, the stretching of the adhesions is the alarm, if you will, that says that stretching is happening, and you’ve looked at what happens in individual stem cells once stretching is sensed.

Interviewee: Cedric Blanpain

So, when the alarms go on, what happens is the stem cells have different choices when they divide. They can give rise to two stem cells. That’s called stem cell renewal. The stem cell can generate a stem cell and a differentiated cell. That’s called asymmetric cell division. And the stem cell can generate possibly two differentiated cells. What happens here, when you stretch the system, you pull more of the stem cells to give rise to two new stem cells.

Interviewer: Benjamin Thompson

So, tipping the balance towards stem cell renewal rather than having them differentiate, which gives a bigger pool which can then ultimately produce the cells that can make up the top layers of the skin, right?

Interviewee: Cedric Blanpain

Exactly.

Interviewer: Benjamin Thompson

I mean we’ve talked about stem cells plural there, Cedric, but it appears that it’s not every single stem cell that this is happening in. It’s not a global response to the stretch.

Interviewee: Cedric Blanpain

When we performed the analysis of individual gene expressions of individual stem cells and other types of cells in the skin epidermis, we found that there was a signature of the skin stretching only in a subpopulation of these stem cells.

Interviewer: Benjamin Thompson

I mean that’s got to be a bit weird, right, because you imagine that if you’re stretching the skin with this hydrogel, all of the stem cells would experience the stretch.

Interviewee: Cedric Blanpain

All the cells, indeed, are receiving the stretch, but only a fraction of the cells respond in a way that they will activate the gene expression programme. Why the other cells do not respond in a similar manner, it’s an interesting question.

Interviewer: Benjamin Thompson

Now, this work is of course done in mice. What do you think needs to be done to look at the relevance in humans?

Interviewee: Cedric Blanpain

It would be to try to get samples from human patients that undergo reconstructive surgery and see whether the gene signature and the different cellular states that we uncover are conserved between mouse and humans.

Interviewer: Benjamin Thompson

And what’s your gut feeling on that, Cedric?

Interviewee: Cedric Blanpain

Ah, I think we have seen a lot of single-cell sequencing from the human skin and we have performed, this year, a lot of sequencing in the different parts of the mouse skin. We believe that there’s a lot of commonalities, much more commonalities than differences, and so I’m expecting that the pathway that we have uncovered here will be conserved from mouse to human. Maybe there’s going to be additional mechanisms, we can find in human, but I think the basic mechanism that we have uncovered here is very likely to be conserved across mice and humans.

Interviewer: Benjamin Thompson

So, you’re work offers some insight into this mechanism of how stretching skin makes new skin grow then. Now, we know that this phenomenon occurs, but how could this insight be used in a medical setting?

Interviewee: Cedric Blanpain

It occurs but probably it can occur more rapidly, and so what would be nice is by understanding what is happening there, by using drugs that activate the pathway, can we improve the skin expansion in humans or can we use this knowledge in a different situation in which also we need to expand the number of stem cells and produce differentiated skin at the same time.

Host: Shamini Bundell

That was Cedric Blanplain from the Université Libre de Bruxelles. Look out for a link to his paper in the show notes.

Host: Nick Howe

Next up, Benjamin Thompson, Noah Baker and Amy Maxmen are here once again to give us the latest coronavirus updates in this week’s Coronapod. In the past, we’ve kept the podcast a coronavirus-free zone, so if you want to skip this segment then make sure you check out the show notes for the timings of everything else that’s coming up. Take it away, Benjamin.

Host: Benjamin Thompson

So, yes, here we go again then. Time for another Coronapod, and as always, I’m joined by Amy Maxmen in the US and Noah Baker in the UK. Hello to you both.

Amy Maxmen

Hi.

Noah Baker

Hi there.

Host: Benjamin Thompson

Today then we’re going to talk about something that’s very central to sort of the scientific enterprise and that has been hit pretty hard by the ongoing pandemic, and that is science conferences and the societies who organise them.

Noah Baker

Yeah, for sure. So, scientific societies are, as you say, the sort of pillar of the scientific establishment, I suppose. They provide grants, they provide support, they provide mentorship, but they also importantly run conferences. I think this pandemic has thrown in to kind of a harsh light the difficulties that societies like this face when you can’t, for example, hold your annual meeting because often they work on a kind of a break-even model, so they really just about manage to keep surviving financially, and a big part of that is often these conferences. So, it’s interesting to think about what that could mean for science but also what it could mean for the societies themselves, if they’re going to be able to weather this storm, as it were. And Ben, you know a bit about this because you used to work for some societies back in the day.

Host: Benjamin Thompson

I did, Noah. You’re absolutely right, and I think there are a few business models. You’ve touched on one there, certainly, the kind of break-even model. Some societies do use their conferences as a way to try and make money to pay for some of the activities you talked about, but obviously, come sort of, what, March time I guess, in many cases, these things were cancelled with days’ notice, and some of these figures that these societies could potentially lose are fairly staggering – upwards of a US$1 million in some cases – through things like lost venue hire, registration reimbursement and so on. And in many cases, these societies will have one big meeting and lots of little satellite meetings as well around one maybe more niche subject and at a stroke, it seems like all of these had to be cancelled and people were scrambling to try and work out what to do next.

Noah Baker

What do you think this is likely to mean going forward? Cancelling the meetings is one thing, but are societies going to survive? Does it depend on the society? I mean I guess it’s probably almost always a ‘it depends’ kind of an answer.

Host: Benjamin Thompson

Yeah, listeners can’t see me doing the kind of hands up, ‘I’m not sure’ motion, but I think you’re right. In some cases, some of these societies publish journals and have some income from that, but some of the very small ones, I think, are going to struggle, and we are going to see potentially some quite severe knock-on effects. I know that a lot of societies use the money they make from conferences to fund, I don’t know, early career researcher grants to travel or to maybe spend a summer in a lab if you’re an undergraduate or what have you, and these could be quite seriously affected.

Amy Maxmen

It seems like that would be such a hard thing. I’m thinking back to when I went to grad school. Especially for early career scientists, meetings really are pretty important just for making those connections that you wouldn’t otherwise have. It’s just such a critical time period. I guess that part would worry me, in addition to, right, the ability to actually fund early career researchers to do things.

Host: Benjamin Thompson

Well, I said at the start that yes, conferences are sort of central in many cases to the scientific enterprise and, Amy, you’re right. That’s where you kind of make these contacts. And I’ve done a little bit of research and I’ve found there was a paper that came out a few years ago looking at what happened when a conference was cancelled in New Orleans in 2012 because of Hurricane Isaac, and this paper suggested a marked drop in collaborations arising between the people who would have attended, which I guess makes sense, but it does seem that cancelling conferences could have a palpable effect on science.

Noah Baker

I have to slightly hold my hands up here and say, unlike the esteemed Benjamin Thompson and Amy Maxmen, I do not have a PhD and have not attended conferences as a scientist –I’ve attended conferences as a science journalist but it’s someone different – and I guess a question for both of you as people that have been there in that guise, is one of the ways that societies have suggested getting around this sort of problem of not being able to have real conferences is to have virtual conferences so you could still meet, but I kind of wonder whether or not virtual conference are going to meet all of the needs you’ve been talking about.

Amy Maxmen

Just thinking about it, yeah, I think the nice thing about putting conferences online is that more people can attend, and I think we’ve got numbers on that, and one of the stories that Nature ran, the American Physical Society said that they had more than 7,000 registrants for their virtual meeting, which is four times their usual number. So, it does seem like more people can go. That’s a plus. You cut down that barrier of cost all of a sudden. But can you have that moment where you talk to the speaker afterwards and get to know them? Maybe somehow, I guess the way to overcome that is people, I guess, would have to be more outgoing about being able to, say, email people from the meeting, but also on the reverse, maybe the people who are later in their career have to be even more proactive about replying to those emails and making themselves available for virtual talks with people, which is kind of a big ask when we’re all busy.

Noah Baker

I suppose another thing to add as well is there is this elephant in the room with conferences which I think a lot of researchers might want to try to politely look the other way about when you talk about the reality, which is that they can have a really big carbon impact, so people travelling around the world to attend conferences. Again, Nature ran some numbers and the amount of carbon that is emitted by researchers going to conferences a year, it’s not unreasonable to think that that comes up to the kind of emission of a small country. That’s just from scientists attending conferences. So, if you make all of your conferences virtual, that’s a hell of a lot of carbon that you’re saving there, especially when, in many of these conferences, climate change is one of the things that’s being discussed quite a lot, and so you can imagine that maybe this is a positive change from a climate perspective, if it were to continue, of course, which I guess is a big question.

Host: Benjamin Thompson

Well, ahead of this then, I did make a bit of a pros and cons list about holding virtual conferences – my opinion of course – but I think they maybe speak to some of the broader issues, and the reduction in carbon emissions was definitely on the pro list, Noah, and Amy, you spoke about cost earlier, and that’s on there too, but there are other things too. Some of the conferences I’ve been to, maybe the more forward-thinking progressive ones, had sort of childcare crèches as well for researchers bringing their kids, and I think it can be very, very difficult if you are a parent, to go to the other side of the world to deliver a talk, so maybe doing these things virtually levels the playing field. Ditto for people with disabilities who maybe struggle in some of these conference venues that aren’t set up in a modern way that allows for everybody to come along. So, I think those maybe are some of the pro aspects. But I come back to the cons, and I think, Amy, you mentioned some there. Is it harder to network? But I think, in some cases, there’s maybe an element of democratisation as well. I was terrified to ask a question of the big eminent scientist on the podium, but if I could type it in on my computer then maybe I’d be more emboldened to ask that question or what have you.

Noah Baker

That could be a double-edged sword though. Speaking as someone who produces content that has YouTube comments underneath, people being emboldened by keyboards is not necessarily always a positive thing, but I’m sure in the context of a conference with an eminent professor giving a talk then that might be very different.

Host: Benjamin Thompson

In many cases, conferences, as we say, have moved online or have been postponed until 2021, but I guess that must raise its own headaches as well. We have been around and around doing Coronapod long enough now that we don’t know what we don’t know, and one of those things we don’t know is when does ‘normality’ come back? When can I spend time in a room with 10,000 other physicists or biologists or chemists talking about science?

Noah Baker

It’s also tricky because you have to make these calls early, right. If you’re a society and you want to organise a conference, that doesn’t get done overnight. You need time to book your venue and every single thing that happens at a conference, and there is a kind of moment where you have to make a go/no go on that. You have to make a decision about whether you’re going to commit financially and risk the loss if things get cancelled further down the line, so it wouldn’t surprise me if conferences are not going to be happening as they were happening for a really long time because it’s going to be hard to make that financial commitment when we have such an unclear future.

Host: Benjamin Thompson

Yeah, I mean I can say with experience, some places are booked, two, three, four, five years in advance, and so, yes, you’re right. What that does to kind of hole in the balance books in the short term, who knows?

Amy Maxmen

I wonder if we’ll start seeing some really creative approaches. For example, early in the Coronapod, I had talked about this COVID testing Slack group with 600+ researchers on it. Could I imagine something similar for a society where, during a conference, they can have a Slack group where they have different channels for different things to discuss, where it is almost like you’re able to make it a little bit more intimate that way. Zoom is kind of one-sided when you get to have a lot of people. So, yeah, maybe there will be some sort of interesting solutions for this.

Noah Baker

A lot of what we’re talking about is ways to sort of make a conference happen in the way that we know conferences happen but virtually, for example, rather than, let’s just change the whole concept of how a conference works at all. So, instead of having one event once a year, why not have a Slack group that’s open for two months that people can access in different timeframes? I think quite often in times of hardship, people come up with their most interesting solutions so watch this space, I suppose, and see what people come up with.

Host: Benjamin Thompson

Yeah, I mean one example where things were sort of thrown together at the last minute was in Colorado, I believe, earlier this year, and you, Noah, spoke to our colleague Davide who had flown out there for the conference and that was cancelled at a couple of days’ notice, and then the sort of attendees jumped into action.

Amy Maxmen

Yeah, that was the American Physical Society’s Spring meeting, and Davide Castelvecchi, one of our colleagues, had gone to the conference as a reporter. He’d arrived and I think it might have been while he was on the plane, there was an email sent out that said by the way, we’re not going to do this conference anymore, but we’re going to try to do some other things. And so, her arrived in Colorado and then went, ‘Well, okay, what do I do?’ He started talking to some people. I interviewed him sort of virtually through Skype back when that was a novelty to do, and he wanted to find out about how this was going to work, and he thought it was really interesting, this sort of virtual conference that was done on the fly. But now, conferences have started to develop a bit more experience with these sorts of things, and then the American Physical Society, as Amy mentioned earlier on, has more subscribers to its virtual conference than ever before, and so it makes you think maybe there could be some kind of wholesale change here. People are learning quite quickly about how to make this stuff work.

Host: Benjamin Thompson

Well, let’s leave it there then, Amy and Noah. Thank you so much, and I hope you’ll join me for the next edition of Coronapod.

Noah Baker

Thanks, Ben.

Amy Maxmen

Thank you.

Host: Shamini Bundell

And we’ll hear more from the Coronapod team soon. Coming up in a minute, we’ll be finding out the latest from DNA-mapping project ENCODE. Right now, though, Dan Fox is back with the Research Highlights.

[Jingle]

Dan Fox

Giving birth can be a painful experience, but not for women with a rare DNA variant that reduces the ability of neurons to send pain signals to the brain. Researchers studied 72 women who had recently given birth for the first time, including some who had not requested any pain relief during their labour. The team sequenced the new mothers’ DNA and found that the women who had forgone pain relief had a higher prevalence of a rare variant of a gene that may help control the activation of neurons. They also tended to feel less pain in subsequent tests. Experiments in mice showed this variant reduces sensitivity to electrical signals, and as a result, it takes stronger contractions to activate pain-sensing nerves in the uterus. The researchers hope that modelling drugs on the protein made by the gene variant could lead to the development of new drugs to manage pain. Read that research in full at Cell Reports.

[Jingle]

Dan Fox

The architects of ancient Greece built temples to last the ages, but they also kept accessibility in mind. Stone ramps found at many sites are thought to have allowed wheeled carts to deliver supplies, but a new paper suggests that many ramps, especially those at healing sanctuaries, served mainly to facilitate access for visitors with impaired mobility. For example, reconstructions of one sanctuary, dedicated to the Greek god of medicine, revealed ramp access to nine small and large structures around the site. The temple’s uncommonly generous supply of ramps could be evidence that they were built mainly with disabled visitors in mind. Evidence such as vase paintings and skeletal remains suggest that ailments that impair mobilities, such as arthritis, were common in ancient Greece. Ramp up your understanding of that paper by reading it in full at Antiquity.

[Jingle]

Host: Shamini Bundell

This week sees the publication in Nature of a huge number of papers relating to the third iteration of ENCODE, a project aiming to identify all the regions in the human genome involved in gene regulation. To find out more about ENCODE, Anand Jagatia has been speaking to one of the researchers who’s been involved in the project from the start.

Interviewer: Anand Jagatia

The human genome is a code 3 billion base pairs long that contains the instructions for our cells to make proteins and, ultimately, us. In 2003, scientists successfully completed the Human Genome Project, managing to sequence every single one of these pairs. But it turns out that was just the beginning. It was like we had the blueprints for how to make a human but no idea how to interpret it. What did this vast series of As, Ts, Cs and Gs actually encode? Researchers now think it contains between 21,000 and 25,000 genes for proteins, but there’s also a huge amount going on in the rest of the genome. For one thing, lots of it doesn’t code for protein at all. It codes for sections of RNA that have a function in and of themselves, and there are at least 1 million stretches of DNA in the genome, known as switches or elements, that are involved in turning genes on or off or changing their levels of expression. Picking up where the Human Genome Project left off, ENCODE, which stands for Encyclopaedia of DNA Elements, is an ambitious project to identify all of these elements and how they affect gene expression. This week, several papers on the third iteration of the project – ENCODE 3 – have been published in Nature. Rick Myers from the HudsonAlpha Institute for Biotechnology in the US has been part of the project since it began. He explained to me why these areas of the genome are of such interest.

Interviewee: Rick Myers

You don’t get to be a liver cell or a neuron by expressing the entire genome. You have some sets of the genes being activated and other being inactivated, and the hope was to identify these switches and what turns those switches on and off in different cell types. So, when ENCODE started in 2003, it was a pilot project really looking at only 1% of the genome, so then the second phase of ENCODE was to do that on a genome-line level, and then ENCODE 3 that we’re talking about now greatly, greatly expanded that so that we’re not only looking genome-wide. We’re looking at a lot of different cell types and starting to learn a whole lot more detail of this atlas, essentially, like a collection of maps, but know putting these maps together so that they make sense.

Interviewer: Anand Jagatia

So, can you give us a sense of the scale of this? How many of these switches have you identified in ENCODE 3?

Interviewee: Rick Myers

So, now, with ENCODE 3 we’ve identified in the human genome, identified almost a million of these switches. There may well be more of them. These are the ones we’ve identified in a few dozen different cell types. As an aside, we also, during this phase, did a mouse ENCODE project. There’s several hundred thousand in the mouse that are identified, and having the interplay between those two organisms’ datasets has been really helpful for interpreting the human genome, for instance.

Interviewer: Anand Jagatia

And part of ENCODE 3 was trying to figure out how these million or so switches affect gene expression when bound by different molecules in the cell, which could be proteins or even RNA. So, what are some of the molecules that you were looking at?

Interviewee: Rick Myers

A big push was on the DNA-binding proteins that are called transcription factors – proteins that bind to DNA or bind to other proteins bound to DNA and turn genes on or off or determine the levels of the genes in different cell types and at different times during development. And there are a lot of them – 1,600 of these means that we put a lot of our genome and the energy made into making cells into controlling when and where all the genes get expressed. In addition to what we call transcription factors, there are other more general DNA-binding proteins that are called chromatin regulators. They play a role in what the whole genome looks like in a particular cell at any time, in terms of opening up regions of the genome for transcription or helping to keep them closed. So, that was another really important part of ENCODE because they bind to many, many more places in the genome than do transcription factors.

Interviewer: Anand Jagatia

So, what form does all of this data actually take?

Interviewee: Rick Myers

So, ENCODE 3 is the first time we actually generated the encyclopaedia, which is freely available to everyone. It has all the annotations that ENCODE has generated to date – genes, the switches, transcriptomes, epigenetics and many different cell types – and it’s organised and meant to be easy to use. So, computational biologists and many creative scientists helped to build tools to take these very large complex datasets and huge numbers of different contexts and get out what you want to look at.

Interviewer: Anand Jagatia

I mean looking back, how does these kinds of datasets and tools that you’ve used to build this encyclopaedia, how do they compare to what you were using back in the 90s when the Human Genome Project was set up?

Interviewee: Rick Myers

It’s fun for me, at least, to look back on the history of this. When we started the Human Genome Project in 1990, the goal was to figure out one person’s or one composite human genome sequence. The truth is we really didn’t know how we were going to do it. The technology was pretty crude back then, and in 1990 the internet didn’t exist or at least we weren’t using it yet, and we were copying data onto floppy disks and providing that to people as much as we could and, of course, in that subsequent 30 years, we’ve had enormous increases in computational ability, and thank goodness we do because the amount of data we have is millions of times more than what we had in 1990.

Interviewer: Anand Jagatia

In lots of ways, this is basic science, really. You’re trying to annotate the genome to figure out what these different elements are and what they do and how they affect gene expression, but scientists are using the data, and there are practical applications too. Have you got any examples you can share?

Interviewee: Rick Myers

Yes, so one of them is a severe gastrointestinal disorder in babies. The cause was unknown, and researchers used ENCODE data to identify particular switches that control the expression of a gene that was suspected to be involved in this terrible disorder in babies. They tested the region and, sure enough, it was involved in regulating the gene in the digestive system, and that actually identified then the cause of this disease that is also probably related to many other similar diseases in children and even some adults. And that example is one of many where being able to understand how the gene is expressed and how the regulation of the gene is controlled has helped to understand and even work their way towards not just diagnosis and prognosis but treatments.

Interviewer: Anand Jagatia

So, ENCODE 3 is now available in the form of this encyclopaedia, but things don’t stop there. What’s happening with the next phase of the project?

Interviewee: Rick Myers

ENCODE 4 is well underway. The goals in ENCODE 4 are greatly expanding the data collection, a lot more cell types are being included, and we’re really working towards analysing all 1,600 transcription factors and all the chromatin marks. That’s some of the major goals. One of the really important parts about ENCODE 4 is actually integrating all of these data types. You don’t have one little element and one protein controlling the expression of a gene. You have a massive group of components that interact to give you that specificity of cell type, when it’s going to be expressed and when it happens during development.

Host: Shamini Bundell

That was Rick Myers from the HudsonAlpha Institute for Biotechnology talking to Anand Jagatia. To find out more about ENCODE 3, look out for the links in the show notes.

Host: Nick Howe

Finally on the show, it’s time for the weekly Briefing chat where we discuss a couple of articles that have been highlighted in the Nature Briefing – that’s Nature’s daily pick of science news and stories. Shamini, what’s in the Briefing this week?

Host: Shamini Bundell

So, this week, I have picked the exciting topic of smallpox, which is a cheery start. Don’t worry, smallpox has gone, but people are still researching it, and the interesting thing about this research is that they are looking for evidence of the smallpox virus in ancient human remains.

Host: Nick Howe

I thought smallpox was a relatively recent thing though – only in the last few hunded centuries or so – so why would they be looking that far back?

Host: Shamini Bundell

Well, how old different viruses and diseases are can be kind of tricky to tell. So, you might have heard of stories relating to paleopathology, so looking for evidence of diseases in bones.

Host: Nick Howe

Not really. So, how would one look for diseases in bones?

Host: Shamini Bundell

Well, obviously, this only works when you have diseases that do impact bones, so quite famously, conditions like leprosy and syphilis. I have done an image search on this. I’m not sure I’d recommend it, but you can actually see the impact in skeletons of where these diseases have started eating away into the bones. And that is all very well for diseases that do impact bones, but more recently we’ve been able to look at DNA as well, and it’s not necessarily ancient, ancient humans that we’re looking at, but over the past hundreds, even thousands of years, looking at the DNA has been able to tell us which diseases have been around recently, which ones have been around for a long time, and the results are sometimes quite surprising. In the case of smallpox, they found evidence of the virus that causes smallpox from humans from 600 AD, showing that the smallpox virus was around then. And also, that’s what they sort of specifically found, but based on them analysing that DNA, they reckon that the virus must have been around and circulating even way before that, even during the fall of the Roman Empire. So, they can start linking which diseases were around and how they started spreading with sort of big historical events and mass migrations of people and things like that.

Host: Nick Howe

Oh wow, so the virus may almost rewrite some aspects of history. That’s really interesting. So, for my story this week, I’ve been looking at how the Earth’s atmosphere rings like a bell.

Host: Shamini Bundell

Okay, you’re going to have to convince me of this one. I feel like I would have noticed to be honest.

Host: Nick Howe

Laughs. Well, when I say the atmosphere rings like a bell, it’s these giant waves that exist in the atmosphere. So, not something you ever really hear or see. It’s more just like vibrations that are similar to like how a bell vibrates. So, for 200 years, this has been thought. It was originally proposed by a French mathematician, Pierre-Simon Laplace, and over the past 200 years since he said it, scientists have validated that this should happen with models, but it’s never actually been observed until now.

Host: Shamini Bundell

You’d have thought if there were giant waves going everywhere, that would be quite easy to detect.

Host: Nick Howe

You would think so, but it’s sort of fallen in this odd area which atmospheric physicists rarely see. So, they normally look at things very, very short-lived like storms and tornados and things like that, or things that are very, very long-lived over years and decades, whereas this seems to happen quite regularly on the span of a day. So, it’s just that it’s never really been observed until these scientists have looked at this enormous dataset from 1979 to 2016, and they’ve looked at how the atmosphere changes every hour within that time period, and by looking with that sort of detail, they’ve been able to see these regularly occurring horizontal waves of warm and cold air that wrap around the world in line with the equator.

Host: Shamini Bundell

Well, there we go. The speedy progress of science – only 200 years to prove this poor guy’s theory.

Host: Nick Howe

Laughs. Yeah, sometimes science happens very quickly, sometimes over centuries, but we get there in the end. Well, Shamini, thanks for chatting to me, and listeners, we’ll put links to everything we’ve discussed in the show notes. If you’re interested in more, but instead as an email delivered daily, then make sure you check out the Nature Briefing. We’ll put a link to that in the show notes as well.

Host: Shamini Bundell

That’s all for this week. But, as always, if you want to get in touch with us then you can reach us on Twitter – we’re @NaturePodcast – or send us an email – we’re podcast@nature.com. Also, a head’s up for you, there will not be a show next week, but keep an eye out because we’ll be back the week after on 12 August. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe. Thanks for listening.