Chemistry World Podcast - March 2011
1.22: Cells as test tubes
3.29: Electrons charge down DNA molecular wire
5.58: Kenneth Dawson on the challenges and success stories of nanotechnology
12.33: Pig power for batteries
14.35: BSE pathogens passed on by air
16.38: Joe Thornton on resurrecting ancient proteins to understand how they have evolved to do their jobs
24.00: Gold going it alone
26.13: Worms' diet the key to coloured silk
29.48: How much will it cost to bring green technologies out of the lab and into market?
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Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.
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Interviewer - Chris Smith
Hello and welcome to the March 2011 edition of the Chemistry World podcast. With me this month are Phil Broadwith, Mike Brown and Elinor Richards and they're here to discuss current carrying wires that are made from DNA. How pig bones can be used to make better batteries and air-borne BSE. There's evidence that the prion protein that causes diseases like CJD can spread through the air. I'll also be talking to this person, who re-animates fossil proteins from the evolutionary past with sometimes surprising results.
Interviewee - Joe Thornton
So, it indicates that there's a real contingency to the process of evolution that the major changes that took place depended on relatively low probability events that could've happened or if history were to take place again, it might've happened completely differently.
Interviewer - Chris Smith
Joe Thornton is at the University of Oregon, he'll be explaining how he unpicks the past later in the program. I'm Chris Smith and this is the Chemistry World podcast.
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The Chemistry World Podcast is brought to you by the Royal Society of Chemistry. Look us up online at chemistryworld dot org.
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Interviewer - Chris Smith
And to kick us off this month, how do you catalyze toxic reactions safely inside cells - Phil.
Interviewee - Phil Broadwith
Okay Chris, well what Mark Bradley and his team have been doing is putting palladium, a metal that's normally toxic inside of cells so that you can do chemistry inside the cells, which the cells wouldn't normally do themselves. The idea at the end of this thing is to be able to do reactions inside cells maybe kind of build components of drugs together, so if you had two halves of a drug which were very soluble and available in a body, but the combined halves wouldn't be then you could give somebody the two halves of the drug and the catalyst and it would make itself inside the body.
Interviewer - Chris Smith
So you're endowing cells with a synthetic ability they wouldn't necessarily, normally have and you can use other benefits of the fact that it's a cellular environment to make stuff.
Interviewee - Phil Broadwith
Yeah, absolutely Chris. I mean a cell as it stands is a massive chemistry factory, there's chemistry going on all the time inside it, but there are certain things that it can't do and one of those things is things like palladium catalyzed coupling reactions like the ones that won the Nobel Prize last year, the chemistry Nobel Prize. So what these guys have done is take polystyrene spheres with a little bit of palladium inside them and the polystyrene has the effect of cancelling out the toxicity of the palladium, it keeps it held in together and stops it poisoning the cells, but still allows it to do the catalysis.
Interviewer: Chris Smith
Does this mean, you have to manually inject these little spheres into every cell you want to do this to, that sounds quite painstaking and quite tricky work?
Interviewee - Phil Broadwith
I think at this stage, we're just talking about cells in a kind of laboratory assay kind of, say, we're not talking about in living organisms at the moment. But the key thing is that the cells survive with the palladium inside and the chemistry does actually happen, which has never been done before.
Interviewer - Chris Smith
Because, normally that palladium would just kill the cell off.
Interviewee - Phil Broadwith
Yeah absolutely.
Interviewer -- Chris Smith
So what reaction were they doing?
Interviewee - Phil Broadwith
The reaction they're doing is called a Suzuki-Miyaura coupling and it's a way of forming a common carbon bond between two molecules. It's a very powerful reaction that's used a lot in medicinal chemistry and drug development and drug manufacture, but the problem is nobody has ever been able to do that kind of thing inside a cell before.
Interviewer -- Chris Smith
We'd certainly want more. Thank you, Phil. Now Mike, talking about inside living cells, DNA as a molecular wire - tell us more.
Interviewee - Mike Brown
Yes Chris. So we're talking about DNA that conducts electricity and using it as a molecular wire as you would in electronics. So Jackie Barton and her team at California Institute of Technology in Pasadena in the US have taken a 34 nanometer strand of DNA which has 100 base pairs and they've passed a low current electricity thorough it and found that the current goes down the DNA rather than around the DNA.
Interviewer - -Chris Smith
Well that was gonna be my next point. How did they know that with something of that sort of scale that the electricity there inputting is actually going down the DNA not just leaking around the outside?
Interviewee - Mike Brown
The experiment they've done is they made a monolayer film of the DNA strands, all standing up, so that they couldn't move and they anchored it to a gold electrode and at the end of each strand, they put a redox probe, which is a molecule that gives a signal if the current is flowing and then they applied the current and the redox probe then gave the signal to say that it was actually flowing through the DNA rather than the buffer solution around it.
Interviewer -- Chris Smith
I suppose this is neat because it shows you can actually input current into DNA because for a long while people have known that DNA repair enzymes, check the integrity of DNA messages by sending electrical signal between the two and if the DNA sequence is wrong or corrupted by mutation then the electrical signal does not make it from one enzyme to the other, so they keep working towards each other doing the repairs. Where do they say this is going though, what's the application of what they've done?
Interviewee - Mike Brown
You've stolen my thunder Chris really because the whole point of this research that Jackie Barton is doing is basically in DNA sensor applications, so they wanted to check that their DNA wasn't mismatched or they weren't breakages in the DNA and one way to do that is what you said, they sent a current down it and if the current doesn't get all the way to the end, then they know there's a mismatch in the middles. They can use it for sensor applications. Another application that could potentially be used with this is in electronics and in chip design. Because 34 nanometers is getting to the same kind of length, as you would use on chips and as you can conduct electricity with this DNA, you could potentially use it in biochips and things like that.
Interviewer - Chris Smith
Thank you Mike and on the subjects of the science of the very small, how is nanotechnology actually impacting on our lives? Kenneth Dawson is the Director of the Center of BioNano Interactions at University College, Dublin.
Interviewee - Mike Brown
Of course, most well known application, I think already is in the making of computers. For many years, companies have been working to make smaller and smaller features, smaller and smaller wires perhaps to put very simply and other devices and computer chips. Now the advantage of making these things smaller and smaller is that the signals that is electrons in these circuits have to travel shorter distances, but the other major advantage of making things smaller in terms of computer chips is that no material is perfect and there are often sort of impurities that bump the electrons as they pass through cells, so if we can make the distance traveled shorter, we bump into fewer things, we lose less energy and the computers don't waste as much energy.
Interviewer -- Chris Smith
Is there any evidence of this actually being manifested, say in use in action like this one?
Interviewee - Kenneth Dawson
Oh Yeah. I mean, every few years, there's a new fabrication process started somewhere called the fab, that industry was well into the nanometer scale some years ago and they're accelerating fast. There are many other applications, which are only now beginning to become viable, I mean they make take another one that's wide seen as important, harvesting of energy from the sun, for example. If you take a lump of something, let's just take butter for the sake of argument and at another fixed mass and you start cutting that into smaller and smaller pieces, although the mass remains the same, the surface area goes up and up and up, in fact eventually when you go down to a nanometer scale, it's not unusual to have an amount of surface area like a football pitch from an amount of material that's a bit closer to my thumb nail. So, there you're creating huge amounts of surface area and therefore anything that you want to get in from outside is more easily done.
Interviewer -- Chris Smith
When you first said, energy and collection, I thought what you were gonna say was batteries because that's of course one area which is also very promising and one area we're really behind -- really aren't we? Because we want electric cars, we want to stop putting these horrible contaminating pollutants into the sky in the form of CO2 from very inefficient combustion engines. The thing that's holding us back are the batteries.
Interviewee - Kenneth Dawson
Absolutely. So there's, obviously I was just about to come to that. So not only are we able to harvest energy better but recent advances in batteries have been nanotechnology enabled and again for reasons not dissimilar to the ones I just spoke about. So, in terms of energy storage, as well as energy harvesting, nanotechnology seems to be the primary breakthrough.
Interviewer - Chris Smith
What do you think is holding things up or is nothing holding things up and it's literally as fast as we can make the discoveries and they're all coming through?
Interviewee - Kenneth Dawson
Things that could hold us up -- one certainly would be a little bit of caution is being.we're seeing a bit of caution in terms of investment , because people are not really comfortable yet about the whole safety issue and how to go forward. I think that's improving; I think we're getting there and I think probably being realistic. You see there might have been a narrow judgement made in the early days, nanotechnology was promoted, perhaps over promised too quickly.
Interviewer -- Chris Smith
Is there evidence that has surfaced so far for nanoparticles doing bad things or have people only been able to show this under artificial circumstances that under very exceptional conditions you can make them do nasty things?
Interviewee - Kenneth Dawson
There are several examples of explicit materials where the concern seems a little bit more highlighted and genuine and they should be investigated, but in a sense that's no different from chemicals, where many chemicals are seen and some are not. There are some particles with specific surfaces that seem to have toxic effects and are actually some people actually, their cells actually make them to try to understand what's it effects are so that we can be sure that they don't happen accidentally in other systems, that would be, for example, trying to create lot of positive charge on the surface of a nanoparticle, this being shown to certainly have negative impacts on cells. I think the one that is probably seen most media attention is connected to carbon nanotubes; the sort of long stick like quality has sort of drawn analogies to things like asbestos. And again there I think that certainly is receiving intense scrutiny and deserves to be shown intense scrutiny, but again the broad understanding currently is that it's only some examples under some conditions. We're going through examples of nanoparticles as much as possible in this community and seeing and checking them before they reach widespread use that does seem to be possible that nanotechnology will be the first truly scrutinised technology to be introduced in the society and rather than simply see this as an exceptional negative, we might be watching as history is being made in a very positive way. I mean one of the questions for us as a society is do we reject things that are new or do we reach the point of which as a society we are able to face them honestly and resolve them and if we learn how to do that I think the society in Europe will be able to benefit from technology, but will be able to benefit safely?
Interviewer - Chris Smith
Which is reassuring to hear.Kenneth Dawson from University College, Dublin.
Interviewer -- Chris Smith
You're listening to Chemistry World, with me Chris Smith. And still to come, how scientists are making coloured silks by altering what the silk worms actually eat. But before that: a different beast entirely. And in fact Elinor, a new way to give batteries much more brunt.
Interviewee - Elinor Richards
Well, there's a scientist called Huang, from Beijing University of Chemical Technology in China and his team -- they've used pig bones, they're cheap and renewable carbon source as an electrode for lithium-sulfur batteries.
Interviewer -- Chris Smith
First of all explain, why do we need new electrodes for these batteries because I thought lithium cells were quite good?
Interviewee - Elinor Richards
Well actually, lithium-sulfur batteries are better than lithium-ion batteries because they've got higher energy density and sulfur is cheap.
Interviewer -- Chris Smith
But what's the problem with them, in terms of the current generation of electrodes they're using in the battery?
Interviewee - Elinor Richards
Within the battery, the sulfur forms polydisulphides during discharge and these react with the lithium anode, so the lithium gets incorporated in the polydisulphide chains.
Interviewer-- Chris Smith:
Oh and gets locked away. So then it can't take part in any further reactions and that reduces the energy density of the battery.
Interviewee - Elinor Richards
Well yes, the problem is lot of the chains dissolve in the electrolyte solution in the battery, so the sulfur is lost. So they can't take part in any more reactions.
Interviewer: Chris Smith:
I see. So why are the pig bones better?
Interviewee - Elinor Richards
Usually porous carbon is used to absorb the sulfur, but this is really expensive to make and the process is quite long and several steps to make the porous carbon. So the pig bones are a cheap source. They were obtained from a food market in Beijing, so it's a.
Interviewer: Chris Smith:
Simply that's not critical to be just as a reasonable local source.
Interviewee - Elinor Richards
Yes. They crushed the bones to a powder and then they heat them to 450 degrees Celsius to reduce them to carbon and then they activate the carbon with potassium hydroxide and this gives them a high surface area so it makes them more porous, and so the sulfur can absorb into them.
Interviewer: Chris Smith:
You presumably grind the bones up before turning them into a battery, so you don't sort of have a bone in the middle of a battery. You make the carbon into a power.
Interviewee - Elinor Richards
Yes, they gotta ground up first.
Interviewer: Chris Smith:
Have they got any actual numbers to prove that this is better?
Interviewee - Elinor Richards
Well they have said that the cycling performance is higher than normal cathodes with compact structures.
Interviewer: Chris Smith:
That sounds encouraging. Thank you very much Elinor. Now Phil. Rather worried about this one. BSE or at least the pathogen responsible for the prion protein doesn't just go in bits of brain being moved from one animal to another or in dodgey hamburgers, you can also pass it on in air.
Interviewee - Phil Broadwith
Well yes, Chris you can. But it's unlikely to actually be a problem in terms of an everyday person catching one of these diseases. What Adriano Aguzzi at the University Hospital in Zurich and Lothar Stitz at the Federal Research Institute of Animal Health in Tuebingen in Germany have done is show that yes it is physically possible to transfer these prion infectious agents in aerosol droplets.
Interviewee - Chris Smith:
I've been to a lecture by Adriano Aguzzi, he sounds to be a brilliant speaker, so what did he actually do about?
Interviewee - Phil Broadwith
What they did was put a load of a mice in a little inhalation chamber and sprayed them with an aerosol of essentially homogenised mouse brain -- brains of mice that were infected with the prion disease and they found that all of the mice in the chamber went on to develop the disease.
Interviewer - Chris Smith:
Did they give any indication when they wrote about this about how many infectious doses that the mice were being exposed to, because that's a pretty unusual scenario isn't it? I mean, that must be fairly mega exposure these animals are getting.
Interviewee - Phil Broadwith:
The thing that the team stresses is very much that is this not a very realistic, real-life scenario and it's not going to be of any concern to general people. The only thing that they think say might need to take a certain amount of heat of it is labs where you're doing a lot of work with brains or in slaughter houses where you've got potential contact with this kind of aerosol and it can build up to a very high concentration. It's certainly not going to be at any kind of concentration that an infected animal or person is going to be breathing out.
Interviewer - Chris Smith
And the root of infection, do they think it goes in via the nose and through the nerves in the nasal linings or lungs, what's the routine?
Interviewee - Phil Broadwith:
What they've said is that the prions come into contact with nerves in the nose and then propagate it directly to the brain.
Interviewer -Chris Smith
Thanks Phil. And after the question of where we all came from and why work the way we way we do.
Interviewee - Joe Thornton
My name is Joe Thornton. I'm on the faculty of the Biology Department at the University of Oregon. I am a molecular evolutionary biologist. I'm interested in the mechanisms by which proteins have evolved new functions over long periods of evolutionary time. So if you look inside our bodies or you look more closely inside our cells, there are thousands and thousands of proteins, each with exquisitely well optimised and slightly different functions, so we're interested in where that diversity came from. So what we do is we actually resurrect ancient proteins as they existed hundreds of millions of years ago, using a combination of computational methods and synthetic biochemistry and then we can do experiments on these resurrected genes and proteins using molecular biological techniques in order to understand what their job used to be and how they did their job.
Interviewer - Chris Smith
So where do you get these ancestral proteins from these fossil proteins if you will in the first place.
Interviewee - Joe Thornton
We start with a very large database of the protein sequences of present-day proteins in species that exist today, so that the many descendants of the ancient proteins that we're interested in. And from that database, we can infer the phylogenetic tree, the tree of relationships among those proteins, the same way that one can use sequence of proteins or genes to infer the relationship among the species - the tree of life. So this is now the tree of proteins and once we have the tree of proteins, we can trace back from the tips, the present-day proteins, to any ancestor on the tree and determine, the most likely sequence at those ancestral nodes, the ones that have the highest probability of giving rise to all of the sequences that we see in our present day world today. So once we know the likely sequence of the ancestral protein, we use biochemical methods to synthesise a piece of DNA that codes for it and then take that piece of DNA, put it into cultured cells and express it and then do experiments on them to figure out what their ancestral function was and then the most existing part of this technique is it provides a platform for studying the evolutionary process and determine the effect of each historical mutation on the function of the protein.
Interviewer - Chris Smith
If you've got one biological process that hijacks another because a certain mutation changes the protein in a certain way and enables it to take on a whole new function, a gain of function if you will and that means that it can then start doing other things that confer some kind of advantage when deployed in a certain way, you can begin to understand, I suppose, how those new things arose.
Interviewee - Joe Thornton
That's exactly right. So we study hormone receptors and we found using resurrected ancestral proteins that it often only takes one or two of the historical mutations that happened long long ago and only takes one or two to radically shift the specificity of the protein from one hormone to another hormone. Big leaps in function could've happened through small changes in DNA sequence and protein sequence.
Interviewer - Chris Smith
Does it also inform looking in the other direction, you're looking backwards and then asking how do we arrive at where we are today. Can we also take the same sort of jumps and look in the forward direction, saying where do the collections of proteins we have today, where could they take us next?
Interviewee - Joe Thornton
Yeah, So, a very interesting finding that we've had is that even though it often only took a couple of major changes to shift the function of the protein, there are often other historical mutations that occurred prior to those function switching mutations that had to be in place for the function switching mutations to be tolerated. So for instance, if we take the function switching mutations and we introduce them into an even deeper ancestor, they may actually break the protein irreparably, so that it doesn't function at all. Only in the actual historical background in which they occurred, can those function switching mutations be tolerated and then they sort of locked into the architecture of the protein from then on. Interestingly, these we call them permissive mutations, these mutations that set the stage for big shift in function, they usually have no affect on the function in themselves. When they're introduced, they don't change the function in any observable way, they simply set the stage for tolerating the big changes that will come later. So, it indicates that there's a real contingency to the process of evolution, that the major changes that took place depended on relatively low probability events that could've happened or if history were to take place again, it might have happened completely differently. That whole idea that our biology is just one of many possible roles of the evolutionary dice that was really a big surprise because most biologists look at a biological system and often think oh, it's so well wrought, it's so complex and all the parts do their jobs so perfectly that it seems as if it has to be the inevitable outcome of evolution, but in fact it's built on a series of chance events guided by natural selection to places that work exquisitely well but could've ended up very differently under different circumstances.
Interviewer - Chris Smith
So what do you think that Charles Darwin himself would've made of this?
Interviewee -Joe Thornton
That's an interesting question, so you know, one of Darwin's -- one of the biggest problems was he had no idea how genetics worked. You know, he didn't have Mendel's results, he didn't know how the offspring inherit many of the traits of the parents and the grandparents and that was central to his theory. Even without that however, his theory of evolution by natural selection and adaptation turns out to be remarkably accurate. So, I think if he could take an introductory biology class, and learn about the way genetics and molecular biology inside cells were, and see what we've discovered about the homology, the relationships between proteins in different species, he would say, aha, this is the mechanism that I was missing and this is an incredible body of evidence supporting my theory and he would be exactly right. I think it would blow his mind in a positive way.
Interviewer - Chris Smith
Joe Thornton from the University of Oregon. More news now and a controversy over gold, Elinor.
Interviewee - Elinor Richards
Back in 2007, Avalino Corma among others, published a paper saying that a gold complex catalyst had catalysed a Sonogashira coupling reaction and it was coupling reaction between iodobenzenes and phenyl acetylenes.
Interviewer - Chris Smith
So, it could've been the gold, but maybe there was something else they were doing the same thing or doing the business as well.
Interviewee - Elinor Richards
Yeah. So, it could've been the palladium impurities as they react in a similar way to gold showed the catalytic mechanism and so Antonio Echavarren's team tried to establish the mechanism in 2010, but they found that the reaction to couple iodobenzenes with phenyl acetylenes with the homogeneous gold complex catalyst just didn't work.
Interviewer - Chris Smith
So what's that? What's the homogeneous gold complex, what did they actually do?
Interviewee- Elinor Richards
The gold is in a complex with cerium oxide, so homogeneous means it's in the same phase as the reactants. So in that reaction, the gold was unable to activate the iodobenzene, so they suggested that palladium impurities were responsible. Corma has published an article that says that gold alone can catalyze the reaction but it's in nanoparticle form and the nanoparticles arise from decomposition of the complex catalyst and Corma has shown that actually the iodobenzene interacts really strongly with these nanoparticles.
Interviewer: Chris Smith
So gold can do the job, but it has to be in its very specific characteristic, or this very specific structure, which is the nanoparticle and that actually gets produced as the reaction goes forward?
Interviewee - Elinor Richards
Well that happens when the gold complex catalyst decomposes, it forms nanoparticles.
Interviewer - Chris Smith
And what Elinor are the implications of this finding? How does this inform our understanding and what are the applications or other ways in which this may be now utilised our understanding with this?
Interviewee - Elinor Richards
It's another step for understanding the mechanism of reaction and Echo Barnes' work shows that there is a difference as well between the way the homogeneous and heterogeneous catalysts are working and he agreed with Corma's findings. So it's another way to look at the mechanism.
Interviewer - Chris Smith
Well on to something slightly softer, now Mike. You always get the best stories. I don't know how you manage it. Silk. You're a very dapper gentleman, you always wear nice, smart, silk type things. I am not sure about what goes on underneath as well but I am sure so, that not rumor around that possibility, what about colouring that silk though. What have scientists discovered now?
Interviewee - Mike Brown
Okay so scientists in Singapore Ming Yong Han's team at the Agency for Science Technology and Research have found a way to colour silk by feeding silk worms the dye.
Interviewer - Chris Smith
Fantastic, but surely people have thought of this before, they must have tried feeding the silk worm stuff before, to see if you can make the silk take on different characteristics and colour surely.
Interviewee - Mike Brown
Yeah that's right Chris, they have. In the past scientists have fed silk worms dyes, to see whether they'll produce coloured silk and it has worked to a certain extent. What they found in the past is that outside coating of the silk, the ceracin is coloured but when you actually take that away and get to the fibroin which is the core part of the silk which is actually used you know to produce clothing and things like that that's actually just colourless, white still. The outside gets dyed rather than the inside which is the bit you want.
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