 Mae'r drws gweithio yw'r drws dr Justin Sullivan. Justin yn y ddweud yw hwnnw a fflaesio'r ddweud yw'r ddweud yw'r roliadau yw'r ddweud yw'r ddweud gyda Ilyw Gall Lleidgins. Dydym hwnnw i'r genio ar bai o'i bai o'r gweithio'r ddweud i'r ddweud i ddechrau'r ddweud o'r ddweud o'r ddweud yn y dyma i'r geniol sy'n ddigon. Justin yn y rhanolwch o'r gwbl yma'r bwysig yma honos yn sella i melech y bydologiaeth i'r Unifesif Canterbury yn 1994, ac i'r Ph.D i'r Unifesif Otago yn 1998. Rwy'n gweithio'r Unifesif Oxford yn y postdoctrwll felw, yn angen i'r newid, yn ymgyrch i'r Unifesif Yorkland yn 2012. Justin. Ieitha i. I went off the plane this morning and wrote my talk shortly thereafter. So, hopefully it will go okay. So we study genomes and when I look around me and I look around this theatre I see a lot of different people. And yet what you'll have is very similar genetic material. Very similar genetic make-up. But it's those variations in that make-up o'r ymwneud i chi i chi i chi'n gweld. Mae gennym ni i gwybod i gynnig o'r ffordd o'i gweithiol a'r hollwch. Yr hwn o'r cyhoedd oedd, ychwanegu hyn yn gyfanffordd. Yn ymwneud i chi i chi, yna yma, yna yma hwn o'r ymwneud i chi, yna ymwneud i chi i chi'ch gweithiol. Yn ymwneud i chi, yna yma yma hwn o'r ymwneud i chi i chi. Mae'r tawtydd yn gweithio'r bai ddechrau cyfnoddol o'ch holl oesaf gyda'n gyfnodd, a'r wych, ac yn effeithio mae'n ddiw. Cynnyddio'r ddweud yn ymlaen i'r ddweud o'i ddweud o'r ddweud. Mae'n ddweud yma'r moddyl dros genedlaethau, ac mae'n ddweud o'r ddweud o'r ddweud o'r ddweud. Mae'n ddweud o'r ddweud o'r ddweud o'r ddweud o'r ddweud. y ffordd y gallu cyfnodd yn yr uned. A mae'r Liggins, y cyfnodd cyfnodd, yn ymgyrch i'r ddweudio. Mae'r ddweudio'r cyfnodd yma yma yma, a'r ddweudio'r ddweudio. Llywododd i'n ddweudio'r ddweudio'r ddweudio'r ddweudio i'r cyfnodd yma yma yma, yna'r ffordd yma yma yn ymgyrch. Felly, mae'r ddweudio'r ddweudio, yna'r olif oed, yng nghyru. Genedd y cynfirmau eich gwirionedd yn ffyrdd yng Nghymru. Rwy'r gwirionedd o'r olygu o'r ysgol yw'r hyn yn dweud bod y bydd yn gwirionedd o'r ddefnyddol. Mae'r ddefnyddol sydd yn ddefnyddio'r ddeunydd, bydd y ddefnyddio'r ddefnyddio'r ddefnyddio yn ddeunydd yn ddeunydd. Felly yn ddeunydd yn ddeunydd yng ngyfnidol yma o ddeunydd. A llwyddi'n ni? Mae'n rhan o'i ddweud. As we put the salt on that, the oil forms a my salt. It forms a cell around the salt. It protects the salt as it goes through the column. When it hits the bottom, the salt is deposited. So not all information is actually encoded in the DNA itself. And in the sequence of DNA, this type of information is not. But inside each of your cells, you have approximately, Sorry, two metres of DNA, roughly this long, okay, in every one of yourselves. Now, if I was to take someone here and mulch them and extract all of their DNA, and ethics tell me I'm not allowed to do that, but if I was to do that and line your DNA up end to end, it would go from here to the sun and back about 300 times, maybe a few more. But it'd still be too small to see, too thin to see, but that's what it would do. Now, every one of yourselves has this two metres of DNA. So, it's stuffed effectively into a container like this, okay, just whacked in there. But in that container where the DNA takes up about 5% of the volume, you have a whole lot of other things. I didn't tell my wife, I was nicking all her decorations there. They're all stuck in the cell as well, and they are key to making it all work. But the thing about this is that it's not a randomly mixed bag. It's not a closed system like this jar. It's an open system. Energy goes into that system, and when energy goes into it, it's used to create structure, to give it order, to maintain that order. And by doing that, we can regulate genes. We create a structure in which things work together in order to give you the characteristics that you have. And a simple way to show this is effectively with these chromosomes, okay. So, I have two chromosomes, and they have an epigenetic mark, okay. And an epigenetic mark is simply something that responds to the environment and is put on top of the DNA and controls the way the DNA is read. Now, if I have two epigenetic marks on this red chromosome, and I have a blue chromosome, and I put them into a nucleus and I fold them up just randomly and create a ball, okay. You'll see that what's happened is the red chromosome has folded around itself, okay, it's intermingling a bit with the blue chromosome, and that's all great. The epigenetic marks have disappeared. But if, and this is where this goes horribly wrong, if I count this nucleus open, okay, I've got to hopefully get this the right way, oh there you go, look at that. What you'll see, okay, is that those red or those green areas, all right, they came together, okay, and they came together at one point here, and now they're linking red and blue and red. And effectively they've created an environment, and it's an environment that traps factors that regulate genes. It makes the genes work consistently, it helps them work consistently, and it helps them ultimately give you your phenotype, your control. But the thing about that is that DNA, just like this, doesn't fold one way. You have approximately 200 different cells in your body, each one of those cells has the same DNA content. If they all have the same DNA content, how can they possibly be different? One way that are different is that it's joined by this ball, okay, it's a green ball, all right, very nice, unless I throw it. Now it's an orange ball, okay. This ball has exactly the same DNA or information content as this green ball, because it's the same thing. All it happens is it refolds one way or another, okay. I would pass it around, I've got two of them, but you guys would probably nick them. Okay, so the balls have the same content, but your cells are the same. You fold the DNA one way, it's an orange DNA, orange cell, fold it another way, it's a green cell, okay. Really cool, nice, simple thing. Now it seems easy to study this if it's a ball, all right, but DNA is not a ball. DNA is in fact a ribbon like structure, a polymer like structure, like these, okay. So what we do here at the Liggins is a very, very simple technique, okay, and we can capture the structure of the DNA in a cell very simply, and I'll illustrate it to you like this. We have two chromosomes and they're contacting each other at one point, okay. So within the cell they actually physically touch each other. Apparently you have to be careful here say that I said that in the States and some people went too impressed. The chromosomes contact each other at one point, okay, here. What we can do is we can chemically tie these things together and then in the lab we take scissors, molecular scissors, and these molecular scissors basically cut up our chromosomes and they cut it up real simple at a whole lot of sites that we know because we know the sequence. What we then do is we take some molecular staples and they come along and they join the ends of these bits of DNA together, okay. We can then remove all the stuff that we put in here and we end up with a circular DNA molecule, but the circular DNA molecule was made up of a bit of white chromosome and a bit of black chromosome, okay. And these two bits of chromosomes are the bits of chromosomes that were contacting each other inside the cell. So from all the three billion base pairs of DNA that were there we can say that one black bit and one white bit were contacting each other in the cell and that's what we do. And by doing that we're able to study whether we have green or orange formations of the DNA and this tells us a lot about your chances of getting obesity, your chances of getting diabetes, about how well you can grow, about cognition and other aspects because the variants that you have in your DNA invariably don't fall in genes. Invariably they sit outside of genes because most of your DNA is not genes. Most of it is what was called junk. Most of the variant fall in that junk region but the key thing about the junk is it's not junk. It's like this little knob here, okay. And what it does is it contacts a number of genes around it physically in space and when it does that it can turn those genes on or turn those genes off and that's the key to understanding a lot of the variation. That's the key to understanding why some of us grow taller, why some of us are shorter, why some of us might be smarter, there's a contribution from the genetic inheritance, why some of us have a higher risk of getting obesity or diabetes. It's an understanding that. Now the cell itself is a bit like this, okay. It's under tension. It's not a soft bag, it doesn't sort of flop around like this. It has structure and this is really interesting to understand, okay. An important thing to understand because cells move in the body and when they move they go through holes. Some cells, your immune cells for example, migrate through pores and those pores that they migrate through are really very small but because your cell has tension if we push on one part of it it changes the structure elsewhere, okay. And that's really very important to understand and it's important to understand because and one of my students, Elsie, is working on this at the moment but it's important to understand because I'll just get rid of this junk. If we have two pieces of DNA and are present in the cell, this black one that has a little loop in it, oh sorry you can't see it, has a little loop in it, held together by a couple of red proteins, okay, here and here. This white one which is held together by blue proteins here and here. If these two regions are actually contacting each other and held together in three dimensions like this, if we change the structure of the cell and the cell like this is under tension so that when we push on one part we change the structure somewhere else, what happens? What happens is you get instant regulation and you get instant regulation because if I take this and do, hopefully this will work, okay, all right, so if I pull this, that looped region is stuck. Oh that's no good. The looped region contacts itself, ah see that's terrible isn't it, okay, the looped region contacts itself that's stuck and what's supposed to happen is this one here is actually supposed to join on as well and the complex changes so that now I have a string of paperclips instead of individual paperclips so what can happen in the cell is that when you squeeze it through a particular tight hole like as an immune cell does when it moves out to a site of infection like what happens when you jump up and down on the spot and the leg all right and you're getting compression in cells in your legs etc you can change complexes you can cause instant regulation so that is what we're trying to understand in terms of a three-dimensional structure of the DNA thank you very much