Nature Podcast

This is a transcript of the 10th March edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com.

Geoff Marsh: This week scaling up quantum mechanics.

John Teufel: Quantum mechanics is usually something people reserve for God-given structures like an atom that I have no control over engineering. So the idea of engineering a circuit they can behave fully quantum mechanically is a very, very powerful tool.

Kerri Smith: And shape shifting proteins break convention to stay flexible.

Tanguy Chouard: If you stay disorganized, like spaghetti, it allows you to adapt to the shapes of many more different partners.

Geoff Marsh: Plus, which planets are in NASA's sights for the next few years of missions. This is the Nature Podcast. I am Geoff Marsh.

Kerri Smith: And I am Kerri Smith.

Kerri Smith: When geneticists want to know why humans differ from other primates, they typically look for unique additions to the human genome. A group based at Stanford University in California took a different approach, looking for regions of the genome all other primates share but humans have uniquely lost. These lost bits of DNA called Conserved Human Deletions let them down some interesting molecular pathways. One is responsible for the increase in human brain size and another for the loss of spine in the human penis and also the disappearance of facial whiskers. Here's Eric Olson speaking to Gill Bejerano about the missing pieces of the human genome. Nature 471, 216–219 (10 March 2011)

Gill Bejerano: So what these regions actually do the hypothesis is that these regions they don't not code for how to make the proteins but they encode genomic agents that control when and where to make each of these proteins. So some of these regions could be as far as the, mega, you know, million bases away than they would still exquisitely control when and where the gene would turn in.

Eric Olson: And that long distance elements that control gene expression is something called an enhancer, yes?

Gill Bejerano: Absolutely.

Eric Olson: Okay so let's focus in on one of the missing enhancers that your paper looks at, it drives the expression of something called an androgen receptor. Why did you choose that gene in particular?

Gill Bejerano: An androgen receptor is involved in many ways in which the human species especially differences between for example the two sexes play out to androgen receptor in its expression patterns. So that for us seemed like a prime candidate and that's why we would pick a deletion next to that gene.

Eric Olson: When you transplanted that deleted region in to mice, you found it was related to something called penile spines. Could you explain what those are and why they exist?

Gill Bejerano: Right, what we did is we took the chimp's version and the mouse version of the enhancer that is uniquely gone in human and we tested that in mouse as you say. And we had two expression patterns, one is for vibrissae the more colloquial name is whiskers and the other one is with the penile spine, so penile spine are these keratinous structures on the surface of the male genitalia of the male penis and when you look at these structures in a broad perspective through the mammalian kingdom for example, you actually appreciate that almost all mammals and primates have those structures on the surface of the penis. The only species in our genomic screen that didn't or doesn't is human, so we're suggesting that androgen receptor is necessary for making these structures. You know, the mechanism for which that loss of the spine has been completely unknown for the last probably, it's been, you know, studied well over 100 years for anthropological reasons as well.

Eric Olson: What is the connection then between these penile spines and whiskers?

Gill Bejerano: Many of the same developmental signalling pathways for example are co-opted repeatedly to make fairly different organs. So you would imagine that if the same pathways are used, you can re-use the same elements as well, just in absolutely different context by now. So this is part of the answer, part of the answer is we think that why and we see that individual elements much like genes can actually pre-evolve in patterning different tissues at different times.

Eric Olson: And in evolutionary terms I mean this is we lost them both, I mean so they are…

Gill Bejerano: Absolutely.

Eric Olson: Yeah, there's some connection now.

Gill Bejerano: But I would say that in this particular case, that the link to the spines with androgen receptor specifically is extremely strong and extremely appealing, the link to whiskers we didn't talk about specifically but androgen receptors seem to be a modulator of whisker links but not to have not so much a necessary component as much as it is with the spine.

Eric Olson: Let's just talk a little bit in evolutionary terms, is there some evolutionary advantage for humans losing these penile spines?

Gill Bejerano: One possible explanation come from experiments that show that when the spine are lost, sensation in the male genitalia is actually reduced and the hypothesis that that would lead to longer copulation time and that in turn better supports somewhat of a monogamous society, this is really one of the major changes in the human lineage that people speculate have caused a range of phenotypic changes, penile spines potentially being one of them. And then this is the second aspect of that is just the mechanics if you like. So, if a female make sure more than one mate and typically that would be the case, you can imagine that with this keratinous structures which look physically like spines when you copulate with the female you can actually try to mechanically make a way with the stiff competition of the previous suitor for example.

Eric Olson: Aside from penile spines you also looked at how missing enhancers actually increase the growth of brain cells, could you explain how that works?

Gill Bejerano: So in that case we were focusing on an enhancer of a gene that itself stops cell proliferation and the question then was if you remove an enhancer gene that stops cell proliferation could you actually get more cells. So that would be a point where less is actually more so that was the other case when some things try to illuminate otherwise where you know removing genomic regions actually allows you to increase phenotypic characteristics for example our brain, you know, certain aspects of our brain are three times as large as those of chimpanzees for example.

Kerri Smith: That was Eric Olson speaking to Gill Bejerano of Stanford University.

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Geoff Marsh: Now the weird rows of quantum mechanics means that an object can be doing two things at the same time. For the most part it only works for atoms and molecules but recently researchers have been scaling up quantum mechanics. For the past year, teams have been putting vibrating devices made of billions of atoms into different quantum states and measuring them as they flutter. It's a tricky business handling the devices because quantum states are extremely fragile. Now physicists at the National Institute of Standards and Technology in Boulder, Colorado have come up with a clever way of handling their device using microwaves. Geoff Brumfiel spoke to John Teufel to learn more. Nature 471, 204–208 (10 March 2011)

John Teufel: You know at a very fundamental level, a vibrating object if it were behaving purely quantum mechanically would in some sense be in two places at once and this is the general picture a lot of people like to draw. For myself there are many other visceral things that naturally happen when you get a quantum regime. You can in fact tell that the vibrations themselves are discrete, there is a fundamental quantum of vibration; then there is a fundamental quantum of light and using these two effects is something that is absolutely what we are after with these measurements.

Geoff Brumfiel: This is a sort of principle you're talking about, I mean I think a lot of people who are listening to the podcast would be slightly incredulous, I mean I think we've all sort of read a bit about quantum mechanics here and there and we know this happens with atoms and you know molecules maybe, but I dare that you can put something big I mean something possibly visible to the naked eye into a state like this. I mean is that really doable?

John Teufel: Yes absolutely, I mean with the scale things we're doing as we were really pushing not to a single atom but something that's billions or trillions of atoms. The question isn't really if they behave quantum mechanically, it's really verifying that they do and you're again pushing it bigger and bigger and further and further and seeing at what point other effects might come into play or other effects that you couldn't measure in a simple atomic system or a single molecule systems.

Geoff Brumfiel: So that's sort of begins to get at this paper, because even if you can't get something into a quantum mechanical state, it's not exactly easy to tell us if it is right, because if you look at it, I mean, I seem to remember looking inside boxes and things in my undergraduate physics and just drawing super positions.

John Teufel: So part of what we are excited about with this new device isn't just that we should be able to prepare this thing in some quantum state but also the same system gives you a very elegant way to measure it and measure it with a sensitivity that's absolutely required if you want to firmly and confidently say that you're witnessing quantum effects.

Geoff Brumfiel: Just briefly I mean why can't you just simply, you know, look at the vibrator or take a direct measurement of it?

John Teufel: Fundamentally, if I want to know where something is by say bouncing something off of it or such as light, I will absolutely affect where this thing is, I will hit it with some force and it will move and it will respond.

Geoff Brumfiel: So how do you then measure this vibrating drumhead without actually measuring it per se without directly taking a measurement of how it vibrates?

John Teufel: So we've created an electrical circuit very similar to the type of circuits that are in your cell phone that work at microwave frequencies and when we excite this circuit with microwave light, it interacts and it, all of a sudden vibrating object affects this circuit in some way that we can really tell. We can use the micro waves to both make the drum move in a certain way and we can listen to the micro waves light to know what the drum is doing to measure its vibrations.

Geoff Brumfiel: If I understand your paper correctly, my understanding is that what makes this circuit unique is that you get a really strong healthy readout of what's going on, on this quantum drumhead, right.

John Teufel: That's right, it's the reader which the vibrations talk to the microwave blade, it's very, very large and that's what we're excited about, both sides, we get this very good readout. All the information about the vibration is really encoded in the light and conversely the light can do a very good job of controlling the vibrations.

Geoff Brumfiel: So what would this actually be used for, does it have any use?

John Teufel: There's lots of things one would imagine, on a very practical side this vibrating drum could be a very, very good sensor so things like displacement, or forces or acceleration or you can even making it a mass sensor where a couple of extra molecules landed on it, it changes the frequency of this drum, at some point the limits on the sensitivity of a classical sensor will be because of quantum mechanics. So, understanding what those boundaries are really pushing to that boundary is the goal of any precision measurement, any type of sensor. On the kind of, more fundamental science side, getting at the actual quantum effects of this relatively large mechanical object is something that the field as a whole is very excited about and we are interested in pursuing what the limits really are.

Geoff Brumfiel: And why are you so interested in the limits?

John Teufel: Quantum mechanics is usually something people reserve for, you know, god given structures like an atom, like a molecule that I have no control over engineering. So the idea of engineering a circuit that can behave fully quantum mechanically is a very, very powerful tool.

Geoff Brumfiel: You sound pretty excited about it.

John Teufel: Yeah, yes but I am a little biased.

Geoff Marsh: That was Geoff Brumfiel speaking to John Teufel and Geoff will be right back with us in a few moments for the news, first though look out, it's the headlines.

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Kerri Smith: A team from California have been exploring the basis of anxiety. We know there is a little brain area called the Amygdala plays a big role in fear and anxiety, but the team wanted to know which exact cells within that area were doing what. They used optogenetics, a method that involves turning cells on and off using light to investigate the circuits in the Amygdala. They found a bunch of cells which when switched on made mice really anxious but when switched off they counteracted anxiety and the mice chilled out. Finding the exact circuit responsible for anxious behaviour will hopefully make it easier to treat clinical anxiety in humans too. Nature (2011)

Geoff Marsh: We should vaccinate now against a likely candidate for the next flu pandemic, says an opinion article this week. In 2009, the H1N1 flu strain jumped from pigs to humans and caused the so called swine flu epidemic, 90 years before that it killed 50 million people in the 1918 Spanish flu outbreak, now we should be worrying about another old virus H2N2, like the Spanish flu immunity to H2N2 has dropped since its last outbreak in humans in the 1960s, meanwhile a version of H2N2 has been lurking in pigs and birds, the authors recommend a routine vaccination campaign to immunize enough people to keep the virus at bay if it makes the jump into humans. Nature 471, 157–158 (10 March 2011)

Kerri Smith: More brain news now, two teams of neuroscientists have mapped visual circuits in the brain in unprecedented detail. To understand how the brain works, you need to know how everything is connected. Kind of like the Facebook approach to neuroscience. But the brain has so many cells and so many connections between those cells that this is a big challenge. Using an electron microscope together with a sophisticated system for slicing the brain, the scientists traced the connections of individual neurons in the mouse visual system. They confirmed previous ideas about how these neurons help mice to see, but they've got bigger ambitions. Next they want to do hundreds more neurons and who knows, maybe one day the whole brain. Nature 471, 177–182 (10 March 2011) ; Nature 471, 183–188 (10 March 2011) ; Nature 471, 170–172 (10 March 2011)

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Kerri Smith: Stimulate you own visual circuits with our beautiful video on those mapping papers that's at http://www.youtube.com/naturevideochannel.

Geoff Marsh: Now joining us again is Geoff Brumfiel back with some news from NASA. Hi Geoff.

Geoff Brumfiel: Hi Geoff.

Geoff Marsh: And we've got bad news for the Glory satellite, what happened?

Geoff Brumfiel: Yeah that's right, the Glory mission was set to launch last week and it did, but shortly after takeoff it crashed into the Pacific Ocean.

Geoff Marsh: So what went wrong with the mechanics?

Geoff Brumfiel: Well, nobody really knows at this point, but it looks like there was a problem with the fairing, which is sort of this protective clamshell that covers the top of the rocket and the satellite, it's supposed to come off part way through the launch and it didn't and what looks like it happened is just it never separated. Now this is weirdly similar to another accident in 2009 with another NASA satellite called the Orbiting Carbon Observatory launched on the same rocket had the same problem. NASA officials say they think it even crashed on exactly the same spot, so it's really bad news for NASA's earth observing program.

Geoff Marsh: Spooky, okay so if the Glory satellite won't sink into the bottom of the Southern Pacific what exactly would it have been doing on this mission.

Geoff Brumfiel: Well, it sort of had two goals, it was supposed to be looking at the total output of the sun, the solar radiant and then it would also looking down at the earth's atmosphere and measuring aerosols, both of these missions are really important for understanding climate change. The solar radiants, the power out of the sun does vary slightly and could affect atmospheric chemistry and the aerosol measurements tell us you, know, what in the atmosphere, what particular matters man made and what is simply natural and it gives a much better handle on how manmade sort of things like ash and dust are actually affecting the earth's climate.

Geoff Marsh: So it sounds like the loss of this satellite is going to have a huge dent on our collection of data, are there plans to build a new satellite to replace this one?

Geoff Brumfiel: You know, that's what happened with the orbiting carbon observatory in 2009, they pledged to build a new one and they are doing that and set to launch in a few year's time, interestingly enough on the same kind of rocket that has now lost two satellites though NASA says that's under review. In this case, given the budget constraints, I would be surprised if we saw another Glory mission, I think this one may just be lost.'

Geoff Marsh: And staying with NASA the Nature news team have been following the planetary science decadal survey, what's been going on?

Geoff Brumfiel: Yeah, that's right, so this is more big news about NASA's spacecraft. This is sort of the planetary science community laying out what they would like to do over the next decade and Mars is high on the list.

Geoff Marsh: So what would they be doing on Mars then?

Geoff Brumfiel: Well, the mission is called Maxi and the idea is to land on the surface of Mars and look for either pre-biotic chemistry sort of very primitive organic chemistry or even signs of life and they also hope it can return a sample from the Martian surface back to earth. It will probably be flying in conjunction with the European Mars mission as well.

Geoff Marsh: Now trips to Mars don't sound like completely new ideas, is everyone in the community backing this or are there other ideas floating around?

Geoff Brumfiel: Yeah, I mean we've been to Mars recently, you know the Spirit and Opportunity Rovers obviously and other missions, and you're right there were other ideas out there, the big one was a plan to go to Jupiter's moon Europa and do a big sort of orbiting mission there.. The problem is cost, it just cost too much money right now and NASA is on a very, very tight budget. The Mars team claims that they can do this for 2.5 billion dollars and by contrast the European mission will cost 4.7 billion, it's just too much money.

Geoff Marsh: Cost decide though, why would it be interesting to go to Europa?

Geoff Brumfiel: Well, there's a lot of interesting stuff that scientists think is going on underneath Europa, you know, the surface is ice but they believe there's actually liquid ocean down there and potentially life I mean it's been a long chat but people wanted to take a closer look for sure.

Geoff Marsh: All doom and gloom so far, give me some good news Geoff.

Geoff Brumfiel: Yes, well I do have some good news which is that the Messenger mission to Mercury is hopefully by the time you listen to this podcast just entering orbit around the planet and this particular probe will be mapping Mercury's surface, it's really exciting for scientists. Mercury has this huge ion core and very little on the outside and they want to know, you know, was it blasted away by the sun or did it naturally lose most of its other rock in a collision with another planet, Messenger should be able to answer these questions.

Geoff Marsh: Thanks Geoff and if you want more news you can find all those stories and more at http://www.nature.com/news.

Kerri Smith: Now we're just about reading to get our groove on with some shape shifting proteins but first here our transatlantic counter pods with 60-Second Science.

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Karen Hopkin: This is Scientific American's 60-second science. I am Karen Hopkin. This will just take a minute. Every villain has his Achilles heel and microscopic scoundrels are no exception. The challenge for those who wish to ward off microbial bad guys is to identify that weak spot. Now, scientists studying the toxoplasmosis parasite think they've done just that. They share the secret in the proceedings of the National Academy of Sciences. The Toxo parasite is similar to the one that causes malaria. So finding a way to prevent these rogues from reproducing is high on researchers to do this. The bugs are tricky to take down, in part because they're unpredictable in the way they multiply. Sometimes they get in and get busy making babies, other times they copy their chromosomes but hold off partitioning them out to their army of offspring until the time is right. This flexibility has benefits but it also has a drawback. The parasites have to keep track of their chromosomes even if they change their minds about how and when to delete them up. Now scientists have discovered a structure, unique to these parasites that keep their DNA in a tidy bundle for thick and thin, find a drug that breaks that bundle and we could destroy these parasite's dubious plans. Thanks for the minute. For Scientific American's 60 Second Science I am Karen Hopkin.

Kerri Smith: A central tentative biology is that what a protein does depends on what it looks like, its function depends on its structure, but the trouble is some proteins just won't conform. They don't have just one unchanging structure, instead they can change their shape some almost continually, which has left scientists wondering how they can function if they weren't sit still. Nature editor Tanguy Chouard has been chasing some of these fidgety proteins around. He has written a feature about them this week, Tanguy thanks for joining me. Published online 9 March 2011 Nature 471, 151–153 (2011) ‌

Tanguy Chouard: Hello.

Kerri Smith: Now could you describe for us exactly what a disordered protein is?

Tanguy Chouard: The simplest way to define it is define it as if it is not regular protein, the way we used to see them until now is structurally, as you just said it means it has a unique and stable structure. There's only one thermodynamically stable structure for that protein and that's the only one that can function and so a disordered protein is a opposite of that, which means it's structure is not unique and it's not stable so it has many possible confirmations and they change over time.

Kerri Smith: And there's a nice turn of phrase in the future, you talk about disordered proteins as being like unlocking a lock with a piece of spaghetti.

Tanguy Chouard : Well, yeah, because that's exactly the problem, is that how do you get molecular recognition if you have no shape. So you have to open the lock with a key and the key is spaghetti where you might try open your door with that.

Kerri Smith: (Laughs)I would rather not. Now when did scientists first began to realize that not all proteins just to have this one fixed structure.

Tanguy Chouard: Strangely enough, isolated cases of proteins that didn't have a unique structure we have to crystallize or we have to study because we are moving around all the time have been accumulating for just as long as proteins have been studied,. But they were pointed to as oddities that we think even as artefacts like you know the guys studying them, didn't know how to work, so they had to bug me.

Kerri Smith: And how many now, I mean that are beginning to become a bit more respected, right.

Tanguy Chouard: That's true we don't know yet they haven't made to text books yet. What has brought attention to the field are more bioinformatic studies that have found some sort of a signature from sequence on the, that could allow them to predict how many of those proteins are there encoded in the genomes even though they were never studied by structural biologists because these are all actually impedes crystallization that's why the databases or structures are truly were largely depleted of anything disordered.

Kerri Smith: Putting those methods together then and their results, how many proteins do people now think are disordered in some way.

Tanguy Chouard: So these figures are given by bioinformatics, they are reliable to some extent. they predict that 40% of human proteins will contain at least one segment that is disordered that is at least 30-amino acid long and then when you go to signalling proteins that's even more 70% of those proteins are disordered to some extent. Some are disordered from beginning to end.

Kerri Smith: No exactly outliers then anymore, can you give us an example of a disordered protein?

Tanguy Chouard: Well I guess the best example would be a protein called P53 because that protein is really world famous.; It's mutated in half of all human cancers and those who study it are totally convinced that that thing is largely disordered not only in the tube but in the cell. It interacts with hundreds and hundreds of proteins and disorders are actually crucial to most of its function and especially the fact that it can interact with so many proteins and work as so-called hub proteins in signaling the work themselves.

Kerri Smith: The disorder then in that case is just giving this protein kind of multiple personalities?

Tanguy Chouard : Right but in very sophisticated ways, so, the most intuitive way is that if you stay disorganized like a spaghetti, it allows you to adapt to the shapes of many more different partners. It's totally versatile and it's extremely promiscuous.

Kerri Smith: What are the benefits are there to being disordered?

Tanguy Chouard: There are disordered segments that fold upon binding their partners and there are some disordered segments that seem to stay durably disordered. The ones that fold upon binding are extremely interesting. Structural biologists will say see you know in the end they fold and they try to claim that this is still the old structural functional dogma but actually it couldn't be further from the truth. The fact that the protein stays unfolded until it binds brings some enormous functional advantages because it makes the binding actually weaker, because it's more demanding to have to get that thing ordered so the thing binds to its partner almost by its teeth and because of that it's extremely intolerant to fault. If the partner is just that less perfect than the normal partner then the thing falls apart, it cannot fall because falling is all cooperative, it's everything at once or nothing. So because of that it's exclusive binding and it's very fast. Exactly what a protein like P53 needs, it needs to bind fast, get out fast and bind many factors and many at once.

Kerri Smith: Those are the ones that you said they fold when they bind with something and then there are this other class that never fold, what's up with that.

Tanguy Chouard: Well, that's more recent and it's even more mind boggling, you know, I mean again, you know, the structural biologists could say that the other ones, you know, in the end therefore, you know, everything is like it used to be. Basically they stay disordered and they stay under a large number of alternative confirmations even in their bound state. So, there are very rare examples yet but we know that they kind of generalize, they are absolutely fascinating and they bring again, you know, some very interesting functional advantages.

Kerri Smith: It seems like the proteins that the field itself is also in flux. I mean not everyone is convinced, right.

Tanguy Chouard: It's a total mess, it was extremely hard to research because there's so much excitement, you know, there's just the same type of excitement that there used to be in the 50's when the first crystal structures came out. But it's a mess, I'm telling you for the moment, very exciting one.

Kerri Smith: An exciting mess, Tanguy Chouard, thank you very much.

Tanguy Chouard: You're welcome.

Geoff Marsh: That's all we've got time for, but join us next week when we will be learning how sperms sniff out their eggy destinations. I am Geoff Marsh.

Kerri Smith: And I am Kerri Smith:

Geoff Marsh: Sunny side up.

Kerri Smith: Over easy.