Chemistry World Podcast - November 2009
02.04 - How bubbles in champagne pack in the flavour
04.30 - Iridescent squid provide inspiration for James Bond's car paint
06.28 - Nobel laureate Tom Steitz talks about fame and the ribosome
10.47 - Tom Blundell on designing drugs for HIV
15.15 - The best evidence yet for water on the moon
17.55 - Element 114 confirmed after 10 years
19.28 - Ben Davis on redesigning nature to diagnose and treat diseases
26.50 - The world's thinnest nanowires
28.58 - Are sex and grapefruit the keys to eternal youth?
31.40 - The chemical conundrum - What acid was used to dissolve Max von Laue and James Franck's Nobel medals to keep them safe during the second world war?
(Promo)
Brought to you by the Royal Society of Chemistry, this is the Chemistry World Podcast.
(End Promo)
Interviewer - Meera Senthilingam
Hello and welcome to the November edition of the Chemistry World Podcast with Matt Wilkinson, Nina Notman and Anna Lewcock. In this month's show, we explore how to make a protein do exactly what you want.
Interviewee - Ben G. Davis
One of the ideas that we would like to play with is the idea that we can take a generic scaffold, a shape of protein that is found quite widely in nature and then decorate it in a way to give it lots of different functions according to what you wanted to do.
Interviewer - Meera Senthilingam
Mastering the art of synthetic biology, Ben Davis, will be explaining how this technology could be used for earlier diagnosis of diseases such as multiple sclerosis and even brain tumours. Also on the way, the potential for the ultimate spy car.
Interviewee - Matt Wilkinson
You could imagine military applications, whereby we would try to create paints that you could switch a camouflaging effect on or off or may be even sort of being spy cars in creating paints, the future for the next James bond car.
Interviewer - Meera Senthilingam
Matt Wilkinson will be investigating how an understanding of squid biology has led to this possibility for the next bond car. Plus we meet one of this year's chemistry Nobel Prize winners to find out about the work that led to this award and just how it feels to be recognized with such an honour.
Interviewee - Thomas A. Steitz
I am sort of overwhelmed, it's great, but the really exciting part for me was the days we were able to peer into the centre of the ribosome and see this amazing structure that we had no idea what it was going to look like.
Interviewer - Meera Senthilingam
Nobel laureate, Tom Steitz, will be discussing his work on the structure and function of the ribosome. That's all coming up on 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)
(02.04 - How bubbles in champagne pack in the flavour)
Interviewer - Meera Senthilingam
First this month, we pop open some bubbly, as scientists have been exploring the chemistry of champagne bubbles, sounds like fun, doesn't it Anna?
Interviewee - Anna Lewcock
Absolutely! We have got researchers from France and Germany, who have been analyzing champagne bubbles to unravel their molecular makeup. They have borrowed a technique from oceanography. So, if you imagine the rolling ocean waves with a white crust of foam and bubbles as they crash to the surface, oceanographers have studied that ocean fizz, and found that air bubbles that were trapped during rough sea conditions, when they burst, they found that the concentration of certain molecules and the aerosols that were released had certain molecules at a concentration much higher than would have been in the bulk ocean. So a few years ago, scientists thought that perhaps there might be some similarities between that ocean fizz and champagne fizz.
Interviewer - Meera Senthilingam
So, who has been looking into this and how did they go about then analyzing the fizz of champagne?
Interviewee - Anna Lewcock
So, its researchers from France and Germany lead by G?rard Liger-Belair and they used a very simple technique really. They used ultra high resolution mass spectrometry to look at the molecular profile of tiny droplets that burst in the air above the surface of sparkling wines, and they did this by holding a microscope slide over a champagne glass, they then rinsed that with methanol and transferred the solution to the spectrometer.
Interviewer - Meera Senthilingam
And so what did they find?
Interviewee - Anna Lewcock
They found that the concentrations of some molecules in that aerosol were up to 30 times higher than the aerosol in that bulk liquid and the bubbles had much higher concentration of surfactant-like molecules. Now, that is not entirely surprising because those kind of molecules, kind of feel at home on that air-water interface so water-soluble 'head' can sit in the wine part, well the hydrophobic 'feet' are safe in the air within the bubble.
Interviewer - Meera Senthilingam
Knowing this now, how have they been investigating or found out more about the experience of drinking sparkling wine?
Interviewee - Anna Lewcock
One of surprising things that they found was the number of flavour molecules within the aerosol. The chemistry of wine is very complex, so when the team compared their results with data about compounds that are known to contribute to wine flavour, they found a whole range of aroma and flavour molecules that get released when these bubbles burst and the aerosols are released. And as the bubbles burst, those molecules are carried to your nostrils and given that we know that aroma and smell plays a contributing role in our taste, these aerosols do play a role in our experience of drinking champagne.
Interviewer - Meera Senthilingam
Okay. Well, thank you Anna. And from sparkling champagne now to shiny proteins and we are looking at iridescent squid, Matt.
(04.30 - Iridescent squid provide inspiration for James Bond's car paint)
Interviewee - Matt Wilkinson
Yes, indeed Meera. Alison Sweeney at the University of California in Santa Barbara and her colleagues have been studying a group of molecules known as reflectins, which are found inside various types of squid and these are the molecules that the squid use to camouflage themselves so they can't be seen.
Interviewer - Meera Senthilingam
So what types of squid are we talking about here?
Interviewee - Matt Wilkinson
So they were originally characterized in Hawaiian bobtail squid but only certain species of squid including the longfin inshore squid have an ability to control when these reflectins as they are known, switched on and off.
Interviewer - Meera Senthilingam
So what are these reflectins and how do they go about making squid iridescent?
Interviewee -Matt Wilkinson
So reflectins are positively charged proteins and normally they would be held apart by electrostatic forces with the positive charges repulsing each other. But what they found was that the iridescence was mediated by acetylcholine and what happens is that the neurotransmitter, acetylcholine, causes them to become decorated with phosphates and then these phosphates are negatively charged. So that once the charges are neutralized, they conglomerate together and become organized in the cell and this then leads to the iridescence that helps the squid keep themselves hidden from their predators.
Interviewer - Meera Senthilingam
So now that the scientists understand how this works, what are the possible applications for this?
Interviewee - Matt Wilkinson
Well, seeing a squid use this to hide from their predators, you could imagine military applications whereby we would try to create paints that you could switch a camouflaging effect on or off or may be even sort of being spy cars in creating, you know, creating the paints, the future for the next James bond car.
Interviewer - Meera Senthilingam
So understanding how squid protect themselves from their predators could help us create our own camouflage technology. Thanks Matt.
(06.28 - Nobel laureate Tom Steitz talks about fame and the ribosome)
Interviewer - Meera Senthilingam
Now last month saw the announcement of this year's Nobel Prize winners and the chemistry award went to Tom Steitz, Ada Yonath and Venkatraman Ramakrishnan for their work on the structure and function of the ribosome and I had the pleasure of speaking to Tom Steitz from Yale University in the United States to find out just why his work on the ribosome was so important.
Interviewee - Thomas A. Steitz
Well, every cell requires ribosomes, without it a cell cannot survive, the ribosome takes the messenger RNA, that has been made by RNA polymerase from the genes encoded in DNA and it translates the messenger RNA into proteins. So all the proteins, well almost all the proteins in the cell are made by the ribosome.
Interviewer - Meera Senthilingam
And so how did you go about finding the structure of this ribosome? So what methods did you use and how did that help you visualize what it looks like?
Interviewee - Thomas A. Steitz
Well, we used a method called X-ray crystallography. What we need to do this is need a crystal and the crystal that we used was pioneered by Ada Yonath, who co-shared this prize and with these crystals it is possible to get the atomic structure. You put the crystal in front of an X-ray beam and in this case it has to be a very intense X-ray beam, indeed we have to use synchrotron radiation and then the X-rays are diffracted off the crystal and gives, what is called Reflections. They are spots that have different intensities and these hundreds of thousands of diffraction spots are recorded by a detector and then a lot of computing goes on after that.
Interviewer - Meera Senthilingam
And in terms of the different molecules and structures that you can visualize using X-ray crystallography, the ribosome, I believe, is actually quite a large structure. So did it involve quite a few different visualizations that were then pieced together to realize what the overall structure was?
Interviewee - Thomas A. Steitz
Well, the ribosome, the large subunit, which we worked on, is about 1.6 million molecular weight. It is about nearly ten times larger than the previously largest molecule structure that was determined. The advantage of protein or macromolecular crystallography is you can look at anything really. I always tell my students that if you could make a mouse hold still, I am sure you could crystallize and solve its structure, and any case you can look at very very large assemblies using X-ray crystallography.
Interviewer - Meera Senthilingam
Now, as a result of this work, though quite a lot of important scientific development happened and stemmed from it, for example, the fact that a generation of antibiotics was born from this. So, how was this information able to help drug design, and in antibiotic design thereafter?
Interviewee - Thomas A. Steitz
Well, what we did was we made complexes with the existing antibiotics, mostly the ones that bind near the peptidyl transferase centre and there are many categories of antibiotics and what you can then notice is that there are different families of antibiotics that bind very close to each other. The ribosome was extremely similar among all organisms, amazingly similar, given its age; however, fortunately there are some differences between human or eukaryotic ribosomes and the eubacterial ribosomes and those are the regions that are targeted by the antibiotics that can be pharmaceuticals, I mean, obviously, you want to kill the bacteria, but not the host, so we could see where those differences lie.
Interviewer - Meera Senthilingam
Just lastly, how do you feel about being given the Nobel Prize for chemistry?
Interviewee -Thomas A. Steitz
I am sort of a overwhelmed, it is great, but the really exciting part for me was the days we were able to peer into the centre of the ribosome and see this amazing structure that we had no idea what it was going to look like.
(10.47 - Tom Blundell on designing drugs for HIV)
Interviewer - Meera Senthilingam
A true chemist there, Tom Steitz from Yale University whose real enjoyment came from his scientific finding rather than this Nobel Prize. Now Tom's findings were made possible, thanks to the technology of X-ray crystallography, which allowed Tom and his colleagues to visualize the ribosomal structure and analyze its function. And another scientist, who has also used this technique for many years, and whose work led to the first, really effective, treatment against HIV is Tom Blundell from the University of Cambridge, whose work in understanding the structure of HIV proteases, enzymes that are vital to the life cycle of HIV, led to the production of protease inhibitors to fight the infection. So I met Tom to discuss this research and find out what new work it led on to.
Interviewee - Tom L. Blundell
Well, we realized that HIV had an enzyme which processes the virus, allows it to mature. We identified that, we characterized it in the lab. It was one of the first genomes we knew completely HIV, so we were able to express the protein in the laboratory, define its architecture and then use that information to target small molecules and that moved very quickly in the 80s, so that in the 90s, we had the first AIDS antiviral, of course there was a big problem with resistance, but these drugs have been very useful in keeping people alive.
Interviewer - Meera Senthilingam
Now when you say, you are able to define the structure of this protease, what exactly was this structure that you then found, which then made drug targets possible?
Interviewee - Tom L. Blundell
Well, it was fascinating, because as we predicted, it looked like the ancestor of some other molecules we have been studying and so we were able to use that architecture to take the drugs we have been developing before and move them very quickly into HIV proteinases as a target.
Interviewer - Meera Senthilingam
But then how did this method actually help you to visualize what this protease look like and therefore know where to target?
Interviewee - Tom L. Blundell
Well, the architecture turned out to have a very well-defined active site, where the enzyme processes and matures the virus proteins and this looked to us to be a very good binding site for small molecules. It had pockets, which we could explore with chemistry and used to get a selective drug molecule candidate.
Interviewer - Meera Senthilingam
You have gone on from this finding now to try and use X-ray crystallography to try and create drug targets or find possibilities for cancer and also tuberculosis.
Interviewee - Tom L. Blundell
Well, what we did in the 80s was to use the architecture to refine and optimize a molecule which started off with the natural substrate. But what we have been able to do over the last ten years is to use our knowledge of genomics to characterize targets which are important for cancer in the human and important for TB in the bacterium.
Interviewer - Meera Senthilingam
What kind of enzymes do you target that will actually lead to a reduction say of a tumour or help relieve symptoms of tuberculosis?
Interviewee - Tom L. Blundell
Well in cancer, it is quite challenging. So we choose enzymes that are important in regulating the growth of the tumour and we know a quite lot about the signalling and regulatory pathways in the cell. With TB, it is much more difficult, although of course, we have many less genes and therefore proteins in TB. The TB can hibernate, it's got a terrible thick wall, it's very difficult to get things in and that is the challenge there.
Interviewer - Meera Senthilingam
Tom Blundell, from the University of Cambridge, explaining how the use of X-ray crystallography has led to greater insight and development in the field of drug discovery. For both antibiotics as Tom Steitz mentioned earlier, and for his own work on HIV, cancer and tuberculosis.
(15.15 - The best evidence yet for water on the moon)
Interviewer - Meera Senthilingam
You are listening to Chemistry World with me, Meera Senthilingam and still to come, we discover the potential secret to eternal life. How to manipulate proteins to help you find diseases and how scientists have created the thinnest nano wires yet! But first we go out to the Moon, where it is pretty certain now that water exists there. Isn't that right Nina?
Interviewee - Nina Notman
Indeed, so these three studies which have been published in the same issue of Science Magazine. There have been three studies from three different spacecrafts that have gone near to the moon surface, so all three of these have found strong evidence for water on the Moon surface by looking at the infrared absorptions.
Interviewer - Meera Senthilingam
So how does looking at infrared let you know that water is present?
Interviewee - Nina Notman
If you see an absorption in the area of around about 3 micrometers, this is an indication of an OH bond which could be of a hydroxy or water.
Interviewer - Meera Senthilingam
What are the three spacecrafts that have been providing information on this?
Interviewee - Nina Notman
So the first one was an Indian spacecraft and it went around the Moon in late 2008 and it was looking at the possible presence of water close to the lunar poles, and after it found the absorptions around about 3 micrometers, some of the scientists were involved in that study, went back to look at some earlier data, that were taken in 1999 on the Cassini spacecraft and again they found the absorption which suggest that water was present and then the scientists in the first study approached Jessica Sunshine, who was involved in fly-by of the Moon, more recently in June 2009 and suggested that Jessica Sunshine's team looked for the same IR bond. So the final team found IR absorptions which verified the earlier results.
Interviewer - Meera Senthilingam
So you have got three piece of evidence here, confirming there is water on the Moon essentially, but how much water are we looking at here?
Interviewee - Nina Notman
We are looking at really quite tiny amount of water, which equates to less than in the soil of the hottest desert on Earth and to put it more simply, if you take one cubic meter of lunar soil and you squeeze out all the water in it, you will only get one litre of water. So, there is some water, but not a huge amount, but possibly enough, if we were considering putting man bases on the moon, to get the water source from there?
Interviewer - Meera Senthilingam
Now how is it thought that water formed?
Interviewee - Nina Notman
Well, the third team are looking at the daily patterns of water in moon and found that that the formation and retention of water was a continuous process and this adds weight to the solar wind theory, which is just one of the theories, as to why there may be water on the moon.
Interviewer - Meera Senthilingam
And what is this theory?
Interviewee - Nina Notman
The theory suggests that the hydrogen ions in the wind as they bang into the rocks on the moon surface liberate oxygen from them in the form of water.
Interviewer - Meera Senthilingam
And so now knowing that this water is on there, all but just a small amount, what can then be done to potentially improve the life of astronauts travelling out there?
Interviewee - Nina Notman
Well, if somebody can come out with a clever way of extracting this to then store the water, then there is potential for a man base on the moon.
(17.55 - Element 114 confirmed after 10 years)
Interviewer - Meera Senthilingam
And from new discoveries on the moon to new discoveries here on Earth, Anna, as a potentially new element has been found?
Interviewee - Anna Lewcock
Yes, the latest potential addition to the periodic table is element number 114. So, Heino Nitsche and a team from the University of California at Berkeley spent eight days smashing a high-energy beam of calcium 48 ions into a plutonium 242 target and they managed to detect two nuclei of element 114.
Interviewer - Meera Senthilingam
Why is it called element 114?
Interviewee - Anna Lewcock
Calcium 48 has eight extra neutrons compared to the most abundant isotopes of calcium, Calcium 40. So when a calcium 48 nucleus collides with a plutonium 242 nucleus, there is a small chance that the nuclei will fuse to create a compound nucleus with a 114 protons.
Interviewer - Meera Senthilingam
And so what type of element is this?
Interviewee - Anna Lewcock
It is a super heavy element and is relatively unstable, but it is one of a, sort of, drip feed of super heavy elements that are being sort of discovered to confirm to hopefully be added to the periodic table.
Interviewer - Meera Senthilingam
So it is a fairly recent discovery and I imagine it must be quite a long process before it is actually confirmed as an official element.
Interviewee - Anna Lewcock
It is. Well, the original discovery by the Russian team was over a decade ago and it takes quite a lot of jumping through hoops before IUPAC, the International Union of Pure and Applied Chemistry will officially recognize an element and allow it to be added to the periodic table, so it still could be quite sometime before we actually see it added at its own box on the periodic table.
Interviewer - Meera Senthilingam
So although it could be a while before it's official, it's good to hear that element such as 114 are still being found today, particularly adding to the group of super heavy elements. Thanks Anna.
(19.28 - Ben Davis on redesigning nature to diagnose and treat diseases)
Interviewer - Meera Senthilingam
Imagine if we could redesign nature and manipulate, perhaps, the proteins of nature to do exactly what we want them to do. Now nature is obviously impressive in its own right, with years of evolution, fine tuning it, but if you could learn from these improvements and make a few adjustments on the molecular level, well, then you enter the field of synthetic biology. And one scientist working in this area with the hope of diagnosing diseases, such as multiple sclerosis at earlier stages is Ben Davis from the University of Oxford and I spoke to Ben to find out how his team are working on this.
Interviewer - Ben G. Davis
We are using many cases of chemistry to make them break bonds to manipulate biomolecules and create novel biomolecules. So proteins that are artificial and have not existed before for example or to create little constructs that might be considered to be things that look a bit like artificial cells and both of those are two examples that you could say, an artificial or a synthetic form of biology.
Interviewer - Meera Senthilingam
So what proteins have you been looking into and changing and manipulating to find out about say, diseases for example?
Interviewee - Ben G. Davis
We are trying to develop chemistries that could be applied in principles, almost in any protein. One of the ideas that we would like to play with is the idea that we could take a generic scaffold, a shape of protein that is found quite widely in nature and then decorate it in a way to give it lots of different functions according to what you wanted to do and one of the scaffolds we have looked at it is one that is referred to as TIM barrel, this beautiful barrel like structure that is found in almost 10% of all known protein structures and then we have dropped things on to, we have played with the structure, we have played with the function using largely chemical methods rather than, sort of more traditional genetic or biological methods.
Interviewer - Meer
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