Chemistry World Podcast -August 2011

1:33 - Rollerball writes electronics straight to paper 

3:30- Dinosaur smile reveals secret to staying cool 

6:05- Julie Forman-Kay reveals that disordered, unfolded proteins are much more functional and much more common than previously thought 

13:00- Cells turned into living lasers with fluorescent protein 

15:27- A cool way to store hydrogen? 

17:59- Peter Wilde talks about how we digest fat and how that can be applied to designer foods that make you feel fuller and help absorb more vital nutrients. 

24:02- Chatty nanoparticles signal the attack on tumours 

27:30- Making smell-o-vision a reality using a polymer matrix   

30:23- Trivia - What connects fishing with photosynthesis?   

(Promo)

Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.

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Interviewer - Meera Senthilingam 

Hello and welcome to the August 2011 edition of the Chemistry World podcast. I am Meera Senthilingam and joining me this month are Andrew Turley, Josh Howgego and Patrick Walter to talk about cells being used as lasers, a new cool way to store hydrogen, using nanoparticles to target tumours and how a little disorder can be a good thing.

Interviewee Julie Forman-Kay

What the new paradigm says is that function can occur at a much earlier stage and disordered proteins before they fold or if they don't fold at all, so intrinsically this sort of proteins can have function without folding.

Interviewer - Meera Senthilingam 

Julie Forman-Kay will be revealing the high level of disorder found in our proteins and how nature has made the most of this later in the show and we will also hear about using rollerball pens to make electronics, how a dinosaur smile is helping solve a paleontological mystery and a new insight into the field of appetite control. So plenty to look forward to in this month's Chemistry World  podcast.

(Promo)

The Chemistry World Podcast is brought to you by the Royal Society of Chemistry. Look us up online at chemistryworld dot org.

(End Promo)

(1:33 - Rollerball writes electronics straight to paper) 

Interviewer - Meera Senthilingam 

And to kick things off, a new way to make electronics using nothing but pen and paper, Andrew.

Interviewee - Andrew Turley   

Right, so what's happened here is a group of the University of Illinois led by Jennifer Lewis have taken out a regular store bought roller-ball pen and filled it up with silver nanoparticles, sort of suspended in a fluid and then they were able to draw electronics straight on to the surfaces, some of the surfaces are paper, some of them fabric, just using the pen writing in the same way as if you were writing an essay just like that. 

Interviewer - Meera Senthilingam 

So but what's the benefit of doing this? So things like printed electronics or electronic inks are being used say in printing technologies and so on to make say transistors or other things like that. So what's useful by it being in a ball-point pen?

Interviewee - Andrew Turley   

So, there's nothing specific about a ball-point pen. It's all just about exploring all the possibilities. What people are interested in are cheap and disposable electronics, sort of things you can just do on your desktop at home, that could be a desktop manufacturing and this shows that there's a lot of flexibility there. There's some very, very basic things used in this particular instance.

Interviewer - Meera Senthilingam 

So, what are they actually been able to make? So what have they used the ball point pen for?

Interviewee - Andrew Turley   

They have done a variety of things, one of which was to make an LED display, so establishing the LEDs on the paper on the surface and then just connecting them up drawing with the pen. They then showed that they could bend and flex this surface to make a ball just demonstrating that there's a lots of different things you can do with this approach. 

Interviewer - Meera Senthilingam 

So, how would you summarize then the main kind of benefits of having it in this format?

Interviewee - Andrew Turley   

It's just a very low cost option, it's a very flexible basic option that's showing that these printed electronics have the potential to be very robust and also it's very cheap and disposable. That's a key factor for anyone looking to commercialize technology later on.

(3:30Dinosaur smile reveals secret to staying cool) 

Interviewer - Meera Senthilingam 

Now moving away from the feature of electronic ink and back to our past, back to the dinosaurs and fossils, which are providing new insight into whether dinosaurs were warm or cold blooded, Patrick.

Interviewee - Patrick Walter

Yes, there's been a long running debate over whether dinosaurs are hot or cold blooded, so whether they're able to regulate their temperatures themselves or whether that just like reptiles like lizards they would rely on a sun to warm them up. So what Rob Eagle's team at Caltech in the US have done is they've been looking at fossils from the Diplodocus family, three different sauropods and they've looked at the teeth to try and determine just whether they were hot or cold blooded.

Interviewer - Meera Senthilingam 

So, what did they actually look at then with these different kinds of samples of these teeth fossils?

Interviewee - Patrick Walter

Right, so they drilled into the teeth and they took some samples and they broke them up to look the 13C and 18O isotopes found in the teeth and the reason they did this is because appetite, they may know all that teeth is made out of. These two isotopes are laid down in different amounts in different clumps according to the temperature that is present.

Interviewer - Meera Senthilingam 

And so what have they have been able to find out and what actual new insight have been provided doing this?

Interviewee - Patrick Walter

Right so, what they've found is that some large dinosaurs actually had temperatures, actually had body temperatures which are comparable to that of modern day mammals about 36 to 38 degrees. So obviously dinosaurs were pretty warm but there's this other possible reasons for this other than just they are warm blooded. So dinosaurs might have been warm blooded due to a phenomenon known as gigantothermy. So this is where you have such large surface area that you lose your heat much, much slower, so species like leather back turtles rely on this to stay warm. So, some models put these dinosaurs having temperature in excess of 40 degrees C, but this new discovery could mean that these dinosaurs had physiological adaptations to actually whisk away some of the heat. So this means that their necks, their tails could be a way of losing excess heat in the way that certain mammals like, certain marsupials like kangaroos do by running blood close to the surface of their skin.

Interviewer - Meera Senthilingam 

So, has this really helped solve the fact that they weren't necessarily cold blooded but they have still the problem of whether they're warm blooded or if they're gigantotherms?

Interviewee - Patrick Walter

Yeah, I mean basically what they run into here is a problem that they can't distinguish between whether the dinosaurs are warm blooded or whether it was down to gigantothermy. So this is going to need more investigation fishing through the fossil records looking at sizes and various other analyses to try and workout find what's happening here.

(6:05Julie Forman-Kay reveals that disordered, unfolded proteins are much more functional and much more common than previously thought) 

Interviewer - Meera Senthilingam 

But still one step further on this long road of mystery. Thank you Patrick. Now we meet a scientist who has discovered a great deal of disorder going on in nature, but it's an organized form of disorder providing function through this disorder all in the form of disordered proteins. Explaining more is Julie Forman-Kay.

Interviewee Julie Forman-Kay

A disordered protein is best understood in contrast to a folded protein. So a folded protein with stable ordered structure can be thought of as having pretty much a single lowest energy ground state and they have specific interactions with each other and a disordered protein is a highly heterogeneous ensemble of different conformation of states that may transiently populate helical or extended structure over different segments. So you have a wide variety of structures which are sampled and inter-converting dynamically in solution. So disordered proteins have interesting preferential structure which relates to their properties but they are not ordered.

Interviewer - Meera Senthilingam 

So, this is really moving away from conventional thoughts on proteins in terms of them only really having a function, kind of, one state folded and got this final structure, but what you're saying here is that earlier on in their formation they've actually got function there too.

Interviewee Julie Forman-Kay

So the traditional paradigm is that there is a discrete line between biological information and biological function. And you know the traditional paradigm said that you know you start with DNA which is information and you go to RNA which is information and you go to the unfolded polypeptide which is being translated on a ribosome which is information and then this magic thing occurs where the protein folds and then you have function. And what the new paradigm says is that function can occur at a much earlier stage and certainly RNA can be catalytic, you know, you have functional RNA enzymes. So RNA is not just information, it is also function and disordered proteins before they fold or if they don't fold at all so intrinsically disordered proteins can have function without folding. People think that oh! this is a new kind of protein so there is a sense that there aren't that many of them but in fact bioinformatics analysis of the human proteome suggests that about half of proteins of human proteins have significant structures of disorder and maybe about 20% of human proteins are fully disordered.

Interviewer - Meera Senthilingam 

So, having kind of identified really that proteins and disordered proteins can function at this earlier stage I guess, could you give an example of some disordered proteins say in our bodies or elsewhere in the environment and how the disordered protein functions there?

Interviewee Julie Forman-Kay

One very nice example of a disordered protein is the protein that's involved in elasticity in our body. That is a protein called elastin.

Interviewer - Meera Senthilingam 

So, this is something that's quite important biologically in our bodies, what role do disordered proteins play here in the function of say elastin and providing say elasticity in our skin and so on?

Interviewee Julie Forman-Kay

In this particular case what you have is an ability to maintain transient fluctuating interactions while the protein is stretched and yet when the protein is let go that it can shrink down and become more compact. So it's the disordered protein itself that has that elastic property. It's a physical-chemical property of entropy basically that derives elasticity in disordered proteins. But I think most of the functional properties of other disordered proteins has to do with their very large surface area that they present for protein interactions.

Interviewer - Meera Senthilingam 

Why do you think that they've evolved, I guess, in this way? So what are the benefits of having this kind of spectrum of function amongst proteins?

Interviewee Julie Forman-Kay

I basically think that physical chemistry dictates that you're going to have that continuum and nature's just going to exploit what's there. But I think the benefit for us in expanding our understanding of what's there is that, you know, we can now have a much more thorough appreciation of many aspects that have, you know, really led to trying to understand evolution. I think there is a lot of principles in terms of understanding post-translational modification where enzymes have to come in and have access to these proteins and if they're buried in the middle of the hydrophobic core of a protein it is not going to happen; but now it's much easier to understand that most of the effects of post translational modification are exposed because they are disordered. And so, you know, I think we can understand a lot more things and we can bring to bear our appreciation of polymer chemistry principles and you know electrostatics, which play a much more dominant role in disordered proteins than they do in folded proteins and there's a whole field opening up now.

Interviewer - Meera Senthilingam 

How are you hoping that we can use this information? So what are perhaps, some of the applications having understood them?

Interviewee Julie Forman-Kay

Once you understand how biologic processes can be regulated by these protein interactions you can design ways to fix things when they're broken. For instance many cancer proteins and many, many diseases have an involvement of disordered proteins on different levels and if you can understand how disordered proteins bind, then you can design drugs more effectively. And so if you understand what the physics is, you know the physical chemistry, then we could better design compounds that could be used for more effective therapeutics for these disordered highly dynamic interactions. 

(13:00Cells turned into living lasers with fluorescent protein) 

Interviewer - Meera Senthilingam 

So, hopefully providing more specificity for our drug design that was Julie Forman-Kay from the University of Toronto. And now from manipulating proteins to manipulating cells and turning them into lasers, tell me more Josh.

Interviewee Josh Howgego

So, basically here's some research which has been conducted by a guy called Seok Hyun Yun and his Post-Doc Malte Gather from Harvard Medical School and to commemorate the, kind of, 50th anniversary of the laser being discovered, they basically thought, hey, let's get a cell and try and turn it into a laser. 

Interviewer - Meera Senthilingam 

And so how did they set about doing this?

Interviewee Josh Howgego

So, what they did is they took a green fluorescent protein or rather they took a plasmid, which is a little circle of DNA which includes for this particular protein and what they did was they put that into a cell and got the cell to manufacture that protein inside of it and then what they could do was they basically used that living cell as the gain medium for a laser so that involves basically taking two mirrors putting the cell in between them and then kind of radiating it with blue light and then the cells--the green frozen protein--will kind of amplify that light and spit it out as a, kind of, sort of, amplified laser source, a kind of very narrow bandwidth light , very high energy and in one direction.

Interviewer - Meera Senthilingam 

So, I guess to set the scene a little bit for this how do lasers I guess generally work and then how is it then being used or applied here?

Interviewee Josh Howgego

Normally if I talked to about this kind of gain medium so the difference here really is that the gain medium is a living thing. In most layers is that they already used like a crystal or a special dye which has certain energy, kind of, wavelength or energy levels rather sorry. and basically what these guys identified was that this particular protein has some of the same characteristics is those, kind of, things. 

Interviewer - Meera Senthilingam 

So, what is their hope that this could be useful for, so they did it to commemorate I guess the laser, but could it have any applications now that they have identified this possibility? 

Interviewee Josh Howgego

Yeah, they did a, kind of, almost as a gimmick. But actually I don't think it is; it has some quite cool applications. So one of the things that they are sort of thinking about is hoping to improve the resolution of the kind of biological imaging. So when you shine kind of radiation onto a person to try and see what's going on like a MRI scan or something, often you get quite kind of blurry images and that's because there's a problem with the radiation penetrating into the body but if you could actually have cells which acted as lasers that problem could be kind of got around but its' a really. It's the first time someone has done it with something living. So it's got amazing in that respect.

(15:27A cool way to store hydrogen?) 

Interviewer - Meera Senthilingam 

Moving from lasers to hydrogen now, more specifically storing hydrogen, something that's been quite a challenge for scientists for years now really but now a simpler, a simple solution I guess to this could be available, Andrew. 

Interviewee Andrew Turley

Right, so hydrogen is of great interest for transport. It's hoped that we can use it because once processed you only get water at the end and the materials they have looked out for storing hydrogen if you're going to use it in a vehicle have not been ideal so far. So what these guys have done is investigated whether or you might use something very, very simple and something very cool which is ice. 

Interviewer - Meera Senthilingam 

So, how have they set about seeing if this is possible?

IntervieweeAndrew Turley 

Right, so this is all theoretical work, modelling they've done on computers and what they've found is that while they were looking at the different phase transitions of ice. They found that as it melts through one of its phase transitions certain structures develop that they might be able to fit hydrogen inside and then you could carry around as ice and then as the ice melts fully you would get the hydrogen back out and would be able to burn that, so probably more likely used in a fuel cell. 

Interviewer - Meera Senthilingam 

Through the modelling how much hydrogen was it possible to store and so what are some of the figures?

IntervieweeAndrew Turley 

Right, so they've managed to store 3.8% hydrogen by weight which is not a bad figure. They've also been able to load that hydrogen at 150 Kelvin, which is quite a good temperature. It's something like -123 degrees C. But there are lots of practical considerations at the moment; one of them being the ice that should be crushed in someway to reveal the underlying structure, the surface doesn't exhibit quite the same structure that you would need for this storage. Also you need a certain amount of gear for carrying it around. But having said that the ice is better than a lot of other traditional materials or materials that have been investigated previously like metal-organic frameworks and carbon nanotubes in that it doesn't need high pressures to load the hydrogen and it doesn't need high temperatures then to release it later. So this is important and a very promising aspect, yes. 

Jingle

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Interviewer - Meera Senthilingam 

You're listening to Chemistry World, with me Meera Senthilingam and still to come a new step in the technology of smell-a-vision. First though have a good understanding of food emulsions and the way they interact with the enzymes in our body during digestion can help in the fight against obesity. Peter Wilde looks into the interface between oil and water in such emulsions and explains just how they're broken down in our bodies.

(17:59Peter Wilde talks about how we digest fat and how that can be applied to designer foods that make you feel fuller and help absorb more vital nutrients) 

IntervieweePeter Wilde 

It's quite a complicated process. There are several different types of lipid-digesting enzymes. They are called lipases. There's one in the mouth which doesn't do an awful lot and there's a gastric lipase in the stomach which begins the whole lipid digestion process. So it breaks down the fatty molecules into its component part so they're ready for digestion. Once the emulsion fat gets into the small intestine then you have the secretion of the pancreatic lipases, which are more complicated. Because the enzyme has to adsorb to the surface of the fat to be able to breakdown the fat itself there maybe other things on the surface of the fat which stops it doing that. So the liver secretes detergent-like molecules called bile salts which strip the surface of the fat and allow the enzyme to adsorb and to breakdown fat. More than 90% of the fats are actually absorbed in the duodenum. And so we're trying to understand how the interface, how the bile salts adsorb at the interface, how the enzyme adsorb at the interface to breakdown the fatty molecules and we're trying to understand that process at the interface so we control it and then maybe delay the digestion for a more slow release of lipids or promote the uptake of the more beneficial lipid compounds like the omega-3 fatty acids and fat-soluble vitamins and such sort of things.

Interviewer - Meera Senthilingam 

So, what have you been able to see so far? So what are some of the mechanisms that you've been able to get an insight into?

IntervieweePeter Wilde 

One is really the reaction of this bile salts and the lipase. We took a typical lipid which coats the fat, lecithin. It's found in eggs and soy beans and all sorts of vegetables and fruits and that's quite surface active and it will coat the surface of the fat. This forms a very condensed film on the surface. When you add the bile salts, we actually got these really nice images; we show that the bile salts breakdown this condensed phase into different domains of more condensed and more expanded areas and then we added the lipase and we found that the lipase actually adsorbed into the expanded areas only, they really didn't adsorb into the condensed phases, that allowed us to understand the bile salts are basically breaking down that interface to allow the lipase to adsorb. And we were looking at a different type of lipid that are called galactolipids and they're found in cereals and leaves and plants and all sorts of fruit and vegetables and they've got quite a big head group which sticks out into the water and they can pack very tightly on to the surface of the fat and we found that they can resist the adsorption of the bile salts, so the bile salts didn't really have any effect on the interface, the enzyme process and the breakdown of the fat was much slower when we used galactolipids. So we are using that now as a basis to go forward for some human trials to hopefully feed some model foods and see if that affects their lipid digestion and their appetite.

Interviewer - Meera Senthilingam 

And so I guess with this knowledge that you've managed to get so far, so you've mentioned that appetite control could be one application and so this I mean given current situations with regards to obesity levels and so on it's a hope that this knowledge could be used in order to say, develop certain types of food or in order to, as you say, control appetite to therefore prevent people overeating or what are the main kind of applications that you're hoping to use this information for?

IntervieweePeter Wilde 

Well, yes that's more or less it, there is a lot of interest in promoting satiety and controlling appetite as a healthy lifestyle. The majority of the obesity problem that we have at the moment is by people consistently overeating small amounts throughout their life. So if you look at the data people are effectively getting fatter, getting bigger with age and the age groups with the largest body mass index is around, sort of, 50 to 60 years old. And so if we can encourage people just to reduce their energy intake by, yeah, only a few percent by controlling appetite so reduces snacking, reduces overeating at meals that sort of thing you can reduce this age related increase in obesity.

Interviewer - Meera Senthilingam 

So, is it a hope then this could be something that could be used reasonably soon when factoring say various foods and kind of to helping people think about what they're eating and controlling their appetite?

 

IntervieweePeter Wilde 

Yes, there are already foods on the market which claim to do this sort of thing as we learn more about those types of foods, they will become, their role in the market and the role in appetite control and weight control will become clearer. Then there are some more fundamental research projects going on like ours where we're trying to understand the actual mechanisms involved so we can optimize the type of food and the composition of the food to maximize this appetite control effect. And in the future because of legislation foods which claim to control appetite will have to provide very strong evidence that they're actually doing that in a clear well defined way and so our research is hopefully contributing towards that knowledge that will provide that evidence.

(24:02Chatty nanoparticles signal the attack on tumours) 

Interviewer - Meera Senthilingam 

Peter Wilde from the Institute of Food Research. And on to nanotechnology now with the use of tag-team nanoparticles to seek out and destroy tumours with the greater specificity than current treatment for cancer, Patrick.

IntervieweePatrick Walter 

So everyone's familiar with the horrible side effects of chemotherapy, the nausea, the hair loss, all the other problems that go with it. So Michael Sailor at the University of California in San Diego has come up with the way to try and reduce the amount of drugs you need to administer in the body and try and get them into exactly the right place using these nanoparticles that communicate to each other.

Interviewer - Meera Senthilingam 

So what are the nanoparticles and I guess how will they set about communicating and what's the communicating signal used?

IntervieweePatrick Walter 

So, the nanoparticles, they divide them into two sets, they created transmitters and they created receivers. So, the transmitters work by hijacking the body's coagulation system. So when these transmitters enter the tumour, these are tumours in mice, human like tumours in mice. The nanoparticles cause the tumour cells to release fibrin and this is a molecule that normally comes together to help form a clot. That's all part of the body's recovery system. So these nanoparticles cause a massive release of fibrin but it's kind of localized the tumour cells, so then these other nanoparticles are receivers. These receivers are able to detect fibrin and they get localized to just where the fibrin is being expressed.

Interviewer - Meera Senthilingam 

So, they're able to communicate in this way, these two nanoparticles, but how do the first set that go out and find the tumour actually find it?

IntervieweePatrick Walter 

Right, well there were two sets of transmitter nanoparticles. So they were gold nanorods that are able to localize to the tumour because of their size and shape they're able to get stuck into the blood vessels of the tumour and there's also an engineered human protein that is able to target tumours in a similar way to the way antibodies can recognize specific antigens in cells in the blood and these kind of things.

Interviewer - Meera Senthilingam 

So, these identify the tumour and they send a message out to their counterpart to come along but how is the tumour then defeated?

IntervieweePatrick Walter 

Right, so when the signal has been sent out, the receiver particles, when the receiver particles pickup onto the fibrin they're localized to the tumour cells. So in one case there is a lysosome with a peptide attached that response to the fibrin and as part of that response the peptide that is attached to the lysosome gets stapled to the building clot. So once in place the lysosome can release the drug that's been impregnated with and in this case that's Doxorubicin.

Interviewer - Meera Senthilingam 

And how effective I guess did they find this method to be in comparison to other treatment possibilities?

IntervieweePatrick Walter 

The nanoparticles, the chatting nanoparticles are much better at localizing to the tumours, so compared with controls that didn't have that transmitters these recei