1 00:00:24,900 --> 00:00:30,060 Herald: So, willkommen zusammen. Heute Abend gibt es den Talk von Andrea über den 2 00:00:30,060 --> 00:00:35,489 "Corona Virus Structural Task Force". Ich bin melzai_a Herald für die Session. Wir 3 00:00:35,489 --> 00:00:40,030 haben einen Signal Angel, Dia, sie wird die Fragen sammeln, die in den Chat 4 00:00:40,030 --> 00:00:45,010 gestellt werden und am Ende gehen wir im Vortrag über diese Fragen. So viel zum 5 00:00:45,010 --> 00:00:51,530 Ablauf. Der Vortrag wird aufgezeichnet. Und ist danach nachträglich verfügbar auf 6 00:00:51,530 --> 00:00:58,223 Media.ccc.de irgendwann in den nächsten Tagen oder Wochen. Und damit würde ich mich 7 00:00:58,223 --> 00:01:01,730 freuen, Andrea, du als Nachwuchsruppenleiterin an der Uni 8 00:01:01,730 --> 00:01:04,670 Hamburg, du hast die letzten zwei Jahre mit den Codona Virus beschäftigt, und 9 00:01:04,670 --> 00:01:09,970 daraus wunderbare Visualisierung gemacht. Wie lief es denn ab und wie sieht Corona 10 00:01:09,970 --> 00:01:12,220 eigentlich aus? 11 00:01:12,220 --> 00:01:17,049 Andrea: Ja, vielen dank! Erstmal danke für die Einladung. Und ja, genau darum geht es 12 00:01:17,049 --> 00:01:27,170 in dem Talk jetzt, was wir die "corona virus structure task force" nennen. I'm 13 00:01:27,170 --> 00:01:30,990 going to give the presentation in English; so that international listeners can also 14 00:01:30,990 --> 00:01:37,460 listen in. But you can ask your questions in, well, any language anyone here speaks. 15 00:01:37,460 --> 00:01:44,690 I understand German, English and Japanese. And I want to start with a quote by Marie 16 00:01:44,690 --> 00:01:52,620 Curie. I know the room Mary is not named after Marie Curie, but she said something 17 00:01:52,620 --> 00:01:57,850 that is very true in this pandemic, which is: "nothing in life, is to be feared, 18 00:01:57,850 --> 00:02:06,570 only to be understood. Now is the time to understand more so that we may fear less." 19 00:02:06,570 --> 00:02:12,110 And indeed, this holds true for the corona virus more than anything, because as you 20 00:02:12,110 --> 00:02:18,190 all know, you cannot see the virus. You can only see it indirectly visualized by 21 00:02:18,190 --> 00:02:25,490 science or you can see the measures against it or you can see ill people. But the 22 00:02:25,490 --> 00:02:31,550 virus itself is invisible. And I'm going to start this talk with questions. There 23 00:02:31,550 --> 00:02:39,290 will be many questions. And the first one is, what does the corona virus look like? 24 00:02:39,290 --> 00:02:44,989 Now you may think, you know, but the reality of it is that even German news has 25 00:02:44,989 --> 00:02:50,499 no idea. And I know that ZDF is now using a different picture, which looks more 26 00:02:50,499 --> 00:02:58,099 similar to what I'm going to show, but it's very wrong as well. This picture? Is 27 00:02:58,099 --> 00:03:02,379 what most people think the virus looks like. And I also brought you like two top 28 00:03:02,379 --> 00:03:09,799 model and models of the virus. One can even make sounds. Any spiky ball of 29 00:03:09,799 --> 00:03:15,519 this days really passes as a corona virus because no one seems to know what the 30 00:03:15,519 --> 00:03:22,519 thing really looks like. Only it's like crowned. And it has spikes. That's the 31 00:03:22,519 --> 00:03:26,700 only thing that all the models have in common. But some things look like you can 32 00:03:26,700 --> 00:03:32,520 just, you know, like they are little Shrek ears type things or have tentacles. No 33 00:03:32,520 --> 00:03:39,539 one really knows. So how do we know as scientists and can viruses, be seen? If we 34 00:03:39,539 --> 00:03:45,249 imagine so, this is an electron microscopic picture of a human hair. It's 35 00:03:45,249 --> 00:03:53,419 0.1 millimeters. It's the length of this line, so the hair is a little bit less. 36 00:03:53,419 --> 00:03:58,040 The little red dot, which you may or may not be able to see inside that circle is 37 00:03:58,040 --> 00:04:02,670 the size of the corona virus. Now if we zoom into the picture of the hair, you can 38 00:04:02,670 --> 00:04:10,279 see, I hope, a little red dot here. And that's the corona virus to measure. So it 39 00:04:10,279 --> 00:04:18,739 is 150 nanometers, or 0.0001.5 mm large. That is tiny 40 00:04:18,739 --> 00:04:26,950 even by scientists sentence. However. Even smaller than the virus with 150 41 00:04:26,950 --> 00:04:32,440 nanometers. It's a single atom, which is represented here again by a 42 00:04:32,440 --> 00:04:40,889 dot, which is barely visible and is 0.1 nanometers in diameter or one. Angstrom. 43 00:04:40,889 --> 00:04:46,620 Atoms are tiny, even compared to the virus. A virus is composed being matter of 44 00:04:46,620 --> 00:04:53,010 very, very many atoms. How can we visualize something this small? Can we see 45 00:04:53,010 --> 00:04:59,840 it with a light microscope? And what color would the virus be? This is to scale. 46 00:04:59,840 --> 00:05:04,580 Yellow light. It is 600 nanometer wavelength meaning from this point to 47 00:05:04,580 --> 00:05:09,650 this, it is 600 nanometers. So the wavelength of visible light, which ranges 48 00:05:09,650 --> 00:05:19,080 from 400 to 780 nano meters, is actually longer than the virus is white. So there 49 00:05:19,080 --> 00:05:27,090 is no chance whatsoever to ever observe a single virus with light just physically 50 00:05:27,090 --> 00:05:33,449 not possible. We need something that has a smaller wavelength, and there are two 51 00:05:33,449 --> 00:05:40,819 things we use X-rays, which have 0.1 nanometer wavelength. So they 52 00:05:40,819 --> 00:05:45,870 are very, very small. They're like light. They're also photons. We call it 53 00:05:45,870 --> 00:05:53,190 also X-ray light (Röntgenstralung, Röntgenlicht). But they have so high energy 54 00:05:53,190 --> 00:05:58,270 that their wavelengths are tiny. The other thing are electrons, which have even 55 00:05:58,270 --> 00:06:02,680 smaller wavelengths. If you choose to regard them not as particles, but as 56 00:06:02,680 --> 00:06:07,739 waves. So we can use electrons and X-rays to observe the virus, and we do. And for 57 00:06:07,739 --> 00:06:12,710 this, we have several possibilities. One of them is large particle accelerators 58 00:06:12,710 --> 00:06:17,199 like the one I'm working on in Hamburg, which produces very intense X-rays. 59 00:06:17,199 --> 00:06:23,080 Another one is an electron microscope. So here is a model of an electron microscope. 60 00:06:23,080 --> 00:06:29,730 In order to use it, you need a scientist and then you shoot an electron beam from 61 00:06:29,730 --> 00:06:34,750 an electron cannon. That's the official scientific term. It's an electron cannon 62 00:06:34,750 --> 00:06:40,909 onto both an electron gun electron cannon electron gun. You shoot your electrons 63 00:06:40,909 --> 00:06:44,760 through lenses, which are magnetic. Electrons are negatively charged so the 64 00:06:44,760 --> 00:06:50,710 magnetic field can be used as a lens system onto a sample. For example, the 65 00:06:50,710 --> 00:06:57,120 virus and then you have a detector. What do we see on this detector? We should 66 00:06:57,120 --> 00:07:03,580 viruses with electrons and record how many electrons pass through the sample? What we 67 00:07:03,580 --> 00:07:07,520 see looks like this. So of course, it's black and white because electrons come. 68 00:07:07,520 --> 00:07:14,740 There's no colors involved. And what you can see is a dark shadow. And then around 69 00:07:14,740 --> 00:07:22,780 it, a little bit of bright spots, almost like a corona during a sun eclipse. So 70 00:07:22,780 --> 00:07:27,879 this is why the corona virus is called corona virus, because it spikes under the 71 00:07:27,879 --> 00:07:34,219 electron microscope look like a corona. And these pictures have no colors, but 72 00:07:34,219 --> 00:07:37,740 scientists like to colored them in particular in order to tell people that 73 00:07:37,740 --> 00:07:42,319 this is a dangerous virus and that is the background. So if we colored, it may look 74 00:07:42,319 --> 00:07:48,810 like this. And this is an official picture released very early in the pandemic by the 75 00:07:48,810 --> 00:07:57,360 National Institutes as one of the first pictures of the new corona virus. We can 76 00:07:57,360 --> 00:08:01,360 also do scanning electron microscopy, which is a similar measure where you coat 77 00:08:01,360 --> 00:08:06,840 the entire surface and then you get a pretty three dimensional picture. What you 78 00:08:06,840 --> 00:08:11,189 can see here are lung cells, the lung carpet like the like hairy structure here. 79 00:08:11,189 --> 00:08:17,960 That's lung cells that are single type two alveolar epithelial cells. So there are 80 00:08:17,960 --> 00:08:23,110 like a little like their job is to get rid of stuff the lungs don't want 81 00:08:23,110 --> 00:08:28,710 there, like a carpet, they can move and they get rid of stuff for you. However, 82 00:08:28,710 --> 00:08:32,830 these cells, you have a problem. They're infected with corona virus. You can see 83 00:08:32,830 --> 00:08:41,040 some slime or mucus here, and you can see the viruses here. Because of the coating, 84 00:08:41,040 --> 00:08:45,680 they look a little bit like cauliflower. So that's nice. But it doesn't give us the 85 00:08:45,680 --> 00:08:50,310 full picture, but so much for people who say we cannot isolate the virus. We can 86 00:08:50,310 --> 00:08:57,860 actually even like, make it visible. So we can make this invisible enemy visible. It 87 00:08:57,860 --> 00:09:02,390 is just a question of having the right equipment and a good sample of the virus 88 00:09:02,390 --> 00:09:07,830 and many hours of work. The virus therefore exists and can be made visible 89 00:09:07,830 --> 00:09:12,400 using electron microscopes or, for example, as a particle accelerator. But 90 00:09:12,400 --> 00:09:16,530 I'm not going to go into detail here. We have not enough time tonight. I'm only 91 00:09:16,530 --> 00:09:25,250 going to talk about electron microscopes here. So what is the virus made of. Those 92 00:09:25,250 --> 00:09:30,260 This is the virus. We're going to talk about this picture later in the talk when we 93 00:09:30,260 --> 00:09:35,080 talk about model a little bit more. But here is one Spike, I think you've all 94 00:09:35,080 --> 00:09:41,530 heard in news from spike proteins, which cover the surface of the virus or the 95 00:09:41,530 --> 00:09:48,820 virion. If we draw this schematically, as Thomas Splettstösser presented for us, he's an 96 00:09:48,820 --> 00:09:54,080 illustrator, burst in Berlin, it looks like this. And then we take only the head 97 00:09:54,080 --> 00:09:58,750 of the spike, which is the region of the spike we know most about, and then comes 98 00:09:58,750 --> 00:10:03,130 an animation that I did. So it's not quite as pretty. If we zoom in, we see the 99 00:10:03,130 --> 00:10:09,730 surface and below that surface we see things represented as a ribbon. However, 100 00:10:09,730 --> 00:10:13,810 we can show this differently. We can show the individual atoms connected to each 101 00:10:13,810 --> 00:10:19,730 other. The problem with this display is that it's really hard to find anything 102 00:10:19,730 --> 00:10:25,560 here. It is super difficult to get an overview with this picture, so we prefer 103 00:10:25,560 --> 00:10:32,470 to show these complicated and fake molecules made up of atoms as surfaces and 104 00:10:32,470 --> 00:10:38,570 ribbons. And this ribbon diagram, by the way, has also been found by a great female 105 00:10:38,570 --> 00:10:42,980 scientist, Jane Richardson, several decades ago, which was quite revolutionary 106 00:10:42,980 --> 00:10:48,519 for my field. So the virus is made up of atoms and molecules, and they are 107 00:10:48,519 --> 00:10:55,060 structures can be found out by NMR, X-ray crystallography and electron microscopy. 108 00:10:55,060 --> 00:11:00,120 For now, this is all I'm going to tell you. We're now going to dive very deeply 109 00:11:00,120 --> 00:11:05,330 into the biology of the virus and what the structures tell us. And then in the end, 110 00:11:05,330 --> 00:11:09,830 I'm going to tell you a little bit more exactly how we actually get from the 111 00:11:09,830 --> 00:11:17,880 measurement to the model, which holds some pitfalls and problems for us. And it's an 112 00:11:17,880 --> 00:11:23,320 area in which I do usually my research. But first, I'm going to talk about the 113 00:11:23,320 --> 00:11:29,220 model, you all know this picture from the CDC, right? And by the way, this thing for 114 00:11:29,220 --> 00:11:33,640 a scientist, this thing is not a virus, it's a variant. It's only the transport 115 00:11:33,640 --> 00:11:38,630 form of the virus, the virus. That's a few more things that are not contained in this 116 00:11:38,630 --> 00:11:44,630 little show. That's just a transport form for its RNA to get into a whole cell. We 117 00:11:44,630 --> 00:11:48,050 call this a variant. But most people, even scientists, can also refer to it as the 118 00:11:48,050 --> 00:11:55,690 virus. So this is the CDC model, right? That's the picture that went all through 119 00:11:55,690 --> 00:12:00,940 the press around the world. That's like THE picture of this pandemic, and it was 120 00:12:00,940 --> 00:12:06,970 made by the CDC very early on by two scientific illustrators there. However, 121 00:12:06,970 --> 00:12:11,950 already then it had some problems. They made it in quite a rash and it has some 122 00:12:11,950 --> 00:12:22,470 errors. So we decided to make a new picture, which looks like this. And. If 123 00:12:22,470 --> 00:12:28,560 you compare it, two pictures, here are the differences. The head of the spike in this 124 00:12:28,560 --> 00:12:33,700 illustration sits directly into the surface, while in reality it is singing 125 00:12:33,700 --> 00:12:42,050 sitting on a long, very bendy like rope like structure that tethers it. So the 126 00:12:42,050 --> 00:12:46,750 virus, the head of the spike, which binds to the host cell, is quite flexible. The 127 00:12:46,750 --> 00:12:51,470 surface is not quite as coarse as shown here. It's smaller. The virus actually 128 00:12:51,470 --> 00:12:58,140 relatively large for a virus, and it's got other proteins swimming in its surface. If 129 00:12:58,140 --> 00:13:04,320 you look exactly, you'll see the virus is also not exactly round. Now we thought 130 00:13:04,320 --> 00:13:07,550 this is not enough. It's nice to have a picture, but wouldn't it be nice if we 131 00:13:07,550 --> 00:13:12,830 could actually touch it? So we made a 3D printable model for those interested. You 132 00:13:12,830 --> 00:13:18,780 can find also all that information on our homepage. I'm going to show you the 3D 133 00:13:18,780 --> 00:13:26,880 model. Let's see. So. This is the virus model. As you can see, the virus is not 134 00:13:26,880 --> 00:13:33,360 exactly round because it's outside, it's very soft. It's like a soap bubble. It can 135 00:13:33,360 --> 00:13:39,140 change its shape quite drastically. It's wobbly and the spikes are actually 136 00:13:39,140 --> 00:13:42,860 stochastic highly distributed. They're not like regularly arranged and they are 137 00:13:42,860 --> 00:13:49,500 swimming in the skin. And there are other proteins in the surface as well, which you 138 00:13:49,500 --> 00:13:55,670 can perhaps see whether they really formed as little flower shapes, we don't know. 139 00:13:55,670 --> 00:14:01,980 And the virus is huge. So this on the same scale, one to one million as a rhinovirus 140 00:14:01,980 --> 00:14:08,510 for the common cold. The corona virus is huge. 20000 base pairs RNA makes it one of 141 00:14:08,510 --> 00:14:15,420 the largest virus genomes we know. And a virus, therefore as soft on the outside, 142 00:14:15,420 --> 00:14:23,720 while rhinovirus has a very hard and rigid shell that is always composed the same. 143 00:14:23,720 --> 00:14:28,440 And we need this model in the hopes that, like other scientists and perhaps schools 144 00:14:28,440 --> 00:14:34,250 would like to print it at home and actually like, get something tangible and 145 00:14:34,250 --> 00:14:39,170 it turned out they did. So we got quite a few requests from people, from child care 146 00:14:39,170 --> 00:14:43,830 facilities and from schools and from other scientists. And even my administration 147 00:14:43,830 --> 00:14:47,850 like to have them printed. One even proposed we may have them as Christmas 148 00:14:47,850 --> 00:14:55,560 ornaments, but I found that a little bit like tasteless. We didn't do it. And like, 149 00:14:55,560 --> 00:15:01,230 just before I left Hamburg, we got a new model. This model is now already a year 150 00:15:01,230 --> 00:15:07,050 old, and in 2021, signs made quite a lot of progress. So we now know there are 151 00:15:07,050 --> 00:15:11,110 fewer spikes and a virus. All in all, it's a little bit smaller, so it's not quite 152 00:15:11,110 --> 00:15:16,020 like this, but perhaps less so. It's not 15 centimeters in diameter. The model is 153 00:15:16,020 --> 00:15:21,300 12, and it is still like potato shaped. It's not round because now what's 154 00:15:21,300 --> 00:15:26,640 important for me to show, and I would have like to show you this model like in front 155 00:15:26,640 --> 00:15:33,160 of the camera tonight, but. It went into the museum, it was the first one we had, 156 00:15:33,160 --> 00:15:37,420 and we brought it to the opening of this exhibition in Hamburg "Pandemierück in ide 157 00:15:37,420 --> 00:15:41,370 Gegenwart" the gigawatt, so you can now see it in the museum and we'll be back in 158 00:15:41,370 --> 00:15:48,840 my office when they have assembled theres. And this also holds true. I'm going to 159 00:15:48,840 --> 00:15:52,560 talk about the task force in the second half of this talk. But one thing that is 160 00:15:52,560 --> 00:15:56,930 really true and what's true for this project as well is the task force is 161 00:15:56,930 --> 00:16:01,220 typically more interested in new communication projects than in all the 162 00:16:01,220 --> 00:16:07,500 pile of stuff we need to finish. You may notice from home. Right. So this is how 163 00:16:07,500 --> 00:16:14,280 our model. Now, let's dive deeper into the thing, because so far we have only talked 164 00:16:14,280 --> 00:16:20,630 about the virion and only about it's outside. So the virion has to spike 165 00:16:20,630 --> 00:16:27,200 proteins on the outside. Two other proteins M and E protein, it has a double 166 00:16:27,200 --> 00:16:34,230 membrane hull, which is very thin and nucleocapsid, which is wrapping the RNA. 167 00:16:34,230 --> 00:16:38,800 The RNA of actually containing the genes for everything that the virus needs in 168 00:16:38,800 --> 00:16:45,950 order to like, take possession of the host cell. So the RNA is the important bit the 169 00:16:45,950 --> 00:16:51,250 virion is transporting and nucleocapsid and everything else kind of packs it and 170 00:16:51,250 --> 00:16:58,710 makes sure it gets into the host cell. And I'm going to show you quickly a video 171 00:16:58,710 --> 00:17:03,850 because I think this is so nice to understand, and it's the answer to the 172 00:17:03,850 --> 00:17:09,600 question why does soap help against corona virus? Because very many, like other 173 00:17:09,600 --> 00:17:15,419 viruses, are relatively hard to wash off, but not corona virus, because it's so 174 00:17:15,419 --> 00:17:20,280 large, it has only a double membrane shell. And this is a very nice video from 175 00:17:20,280 --> 00:17:25,280 the protein data bank from our colleagues there. So this is the virus double 176 00:17:25,280 --> 00:17:31,430 membrane. It has lipid molecules. You can see there are hydrophobic on the inside 177 00:17:31,430 --> 00:17:36,270 and hydrophilic on the outside, so they lock water on the outside, but not the 178 00:17:36,270 --> 00:17:42,600 inside. Green molecules are soap. Soap also has a hydrophobic tail and a 179 00:17:42,600 --> 00:17:48,280 hydrophilic head. So unlike the water which stays outside the soap just gets 180 00:17:48,280 --> 00:17:54,280 into the membrane and kind of like goes in between the lipids. And then they make 181 00:17:54,280 --> 00:18:01,040 whole sort of water molecules can get inside the virus. They can even assemble. 182 00:18:01,040 --> 00:18:09,550 In around bits of the membrane and get it out of the virus hull or around a spike 183 00:18:09,550 --> 00:18:16,280 and remove to spike, which is hydrophobic to stock out of the virus. This leads to a 184 00:18:16,280 --> 00:18:21,340 total decomposition of the membrane and therefore it can be completely dissolved 185 00:18:21,340 --> 00:18:27,640 by soap. As soon as the nucleocapsid and an RNA are exposed, the virus is no longer 186 00:18:27,640 --> 00:18:34,610 infectious. It needs a spike in order to infect so, you don't need to disinfect 187 00:18:34,610 --> 00:18:39,980 your hands. You can just wash them with soap, which I find is so lucky in this 188 00:18:39,980 --> 00:18:44,410 pandemic because, you know, it would be really ugly if we would need to disinfect 189 00:18:44,410 --> 00:18:50,230 everything all the time, but we can actually just use soapy water. Although, 190 00:18:50,230 --> 00:18:55,750 let's be honest, I like to use disinfectant every here, and then it gives 191 00:18:55,750 --> 00:19:01,250 me just a feeling of more safety. It's kind of like a ritual to protect me. I 192 00:19:01,250 --> 00:19:09,910 suspect several of you are the same. So, so much for the virion, that's like the 193 00:19:09,910 --> 00:19:17,560 outer shell, that's like the transport form. But there is more much more. This is 194 00:19:17,560 --> 00:19:21,140 the corona virus life cycle, or I should be more correct. It should be called 195 00:19:21,140 --> 00:19:25,900 infection cycle because technically speaking, viruses are not life. They need 196 00:19:25,900 --> 00:19:31,520 a host cell to reproduce. So we're going to come back to this picture. We're going 197 00:19:31,520 --> 00:19:40,270 to take this apart bit by bit. First of all, there is entry entry into oh yeah. 198 00:19:40,270 --> 00:19:44,560 Let's quickly go back. The thing at the bottom here, the big thing here. That's 199 00:19:44,560 --> 00:19:48,510 the host cell. And a little one is the virus, right? We're clear on that 200 00:19:48,510 --> 00:19:51,610 Holbrook's here, right? And is the outside. So this is like your lung 201 00:19:51,610 --> 00:19:56,640 outside. That's your lung cell inside or hopefully not your lung cell, right? 202 00:19:56,640 --> 00:20:04,340 There's the virus. And this is the spike, the spike as a vaccine target, as you 203 00:20:04,340 --> 00:20:10,270 know, it's what's encoded in RNA vaccines and it's also contained in all the like 204 00:20:10,270 --> 00:20:17,440 vector vaccines we see. And I brought you another model for that, which saw the 205 00:20:17,440 --> 00:20:28,680 picture here. So this is one to 10 million scale model of the spike. And this is an 206 00:20:28,680 --> 00:20:36,440 antibody. Now if you are vaccinated either by RNA or by a vector vaccine, your body 207 00:20:36,440 --> 00:20:42,110 overproduce as far as injected with spikes, which are usually on something to 208 00:20:42,110 --> 00:20:48,950 carry it a host cell or a cell of your body if it's an RNA vaccine or a vector. 209 00:20:48,950 --> 00:20:54,290 Your body needs a few days to recognize this thing, so once it has, it will build 210 00:20:54,290 --> 00:21:00,290 antibodies that perfectly fit onto that they can recognize the spike very, very 211 00:21:00,290 --> 00:21:04,190 exactly. They have a specific binding site, which is much more rigid than 212 00:21:04,190 --> 00:21:11,090 anything else the antibody can bind to. Then this gets decomposed because the 213 00:21:11,090 --> 00:21:16,260 vaccine is not viable. What remains in your body is information for these 214 00:21:16,260 --> 00:21:24,200 antibodies. So now if you get infected with corona? The immune system antibody 215 00:21:24,200 --> 00:21:28,710 recognizes the spike it has previously seen in the vaccine, and that is how the 216 00:21:28,710 --> 00:21:35,930 vaccine actually works. So having this protects you, one of the biggest problems 217 00:21:35,930 --> 00:21:41,140 with COVID 19 infections is that the immune system responds too late. And then 218 00:21:41,140 --> 00:21:47,730 too much. So having these makes much more certain that you will not get severe 219 00:21:47,730 --> 00:21:55,960 COVID, which is, I think, very nice. And what we also did, together with the 220 00:21:55,960 --> 00:22:01,720 animation lab in Utah is not only make those life life cycle or infection cycle, 221 00:22:01,720 --> 00:22:06,130 we also made an animation the scientifically most accurate animation 222 00:22:06,130 --> 00:22:11,850 available on how the virus actually binds onto the whole cell. There's a lot we 223 00:22:11,850 --> 00:22:18,450 don't know, but everything we do know we have shown here. So here is the virus. You 224 00:22:18,450 --> 00:22:26,320 know the spike protein already. Yes, nucleocapsid inside there is RNA, which 225 00:22:26,320 --> 00:22:32,220 encodes for the rest, we're going to go into the rest after this. And then at the 226 00:22:32,220 --> 00:22:37,820 bottom here is the host cell. So lung cells actually have ACE2 receptors shown 227 00:22:37,820 --> 00:22:43,750 in purple, and a spike protein recognizes those specifically meaning that items like 228 00:22:43,750 --> 00:22:53,840 a puzzle piece fit exactly onto the purple receptors on the lung cells. The spikes 229 00:22:53,840 --> 00:23:01,710 bind there and then something else happens. Another enzyme also being in the 230 00:23:01,710 --> 00:23:07,220 membrane of the host cell cuts the spike, so it's not like the name spike suggests 231 00:23:07,220 --> 00:23:12,320 it would like shoot something into. But that's not the case. It gets cut and then 232 00:23:12,320 --> 00:23:16,250 comes to bed where we are a little bit unclear how this happens. So what we know 233 00:23:16,250 --> 00:23:20,300 is after it's cut, it somehow ends up being tethered into the host cell and we 234 00:23:20,300 --> 00:23:24,870 don't know the mechanism of this. So we decided to illustrated here with like a 235 00:23:24,870 --> 00:23:31,480 refolding process and then it's energetically unstable. So in order to 236 00:23:31,480 --> 00:23:36,470 become more stable, the whole thing clamps and folds together, thereby dragging the 237 00:23:36,470 --> 00:23:41,820 virus and the host cell membrane together, the two membranes to buy a lipid membranes 238 00:23:41,820 --> 00:23:49,560 Fuze. The virus material is inserted into the cell. The RNA is now inside the host 239 00:23:49,560 --> 00:23:57,050 cell, and this is how infection happens. So we felt it was particularly important 240 00:23:57,050 --> 00:24:01,930 to show this to people. We have made this animation Creative Commons, but 241 00:24:01,930 --> 00:24:06,160 unfortunately only American television caught up on it, so we're really hoping 242 00:24:06,160 --> 00:24:10,250 that one of the German like documentaries will show this, because we think it's 243 00:24:10,250 --> 00:24:19,870 really nice to see this process like as accurately as we can depicted. So here is 244 00:24:19,870 --> 00:24:24,809 the spike. That's the role of the spike. Now the nucleocapsid, an RNA a half 245 00:24:24,809 --> 00:24:32,760 entered into the host cell. What happens now is that the nucleocapsid dissolves. 246 00:24:32,760 --> 00:24:38,170 How that exactly happens, we don't know, but it dissolves and RNA gets immediately 247 00:24:38,170 --> 00:24:45,030 translated into protein. So the genome gets RET inside the cell because the cell 248 00:24:45,030 --> 00:24:49,700 believes it's own either comes from the host cell and it starts building. The 249 00:24:49,700 --> 00:24:54,100 proteins encoded in proteins are again molecules. And actually, it makes one 250 00:24:54,100 --> 00:25:00,600 very, very long protein chain really long, which is called the poly protein, which 251 00:25:00,600 --> 00:25:06,590 then gets cleaved. So D'Souza's in this case, the thing that cleaves all the long 252 00:25:06,590 --> 00:25:11,610 protein chain into individual molecules that don't actually can work is called the 253 00:25:11,610 --> 00:25:16,970 main protease because it's cutting protein that's called the protease. And these are 254 00:25:16,970 --> 00:25:22,150 the little triangle shaped things here. Only when that happens to these bits 255 00:25:22,150 --> 00:25:26,890 become functional. So if it doesn't happen, if we can like hindered this like 256 00:25:26,890 --> 00:25:33,010 cutting off the long polypeptide chain, we have an efficient drug against corona, 257 00:25:33,010 --> 00:25:37,880 which is why main protease is a major drug target. And what you can see here in red 258 00:25:37,880 --> 00:25:44,510 is the drug actually bound two main protease. So that's what it looks like. We 259 00:25:44,510 --> 00:25:48,220 are looking specifically for inhibitors, which will stop this molecule from 260 00:25:48,220 --> 00:25:52,150 function. So you can imagine this like a screwdriver that we put out of right point 261 00:25:52,150 --> 00:25:57,910 in a machine where it fits and it stops the entire machinery. That's what we want. 262 00:25:57,910 --> 00:26:01,610 And that's like called structure based drug design. When you actually know the 263 00:26:01,610 --> 00:26:06,220 structure of the molecule and then you find a molecule, a small molecule, a drug 264 00:26:06,220 --> 00:26:13,221 molecule that specifically stops whatever that protein molecule is doing. It's also 265 00:26:13,221 --> 00:26:21,230 how many antibiotics work or, for example, if you've been up long yesterday aspirin. 266 00:26:21,230 --> 00:26:29,310 Then. From here, where we have the poly protein thing. Something happens inside 267 00:26:29,310 --> 00:26:33,830 the cell, the cell is making some kind of foam, which is connected to the 268 00:26:33,830 --> 00:26:39,940 endoplasmic reticulum. That's just warm and inside it. These like enzymes that 269 00:26:39,940 --> 00:26:44,330 have now been cut in our functional start, like a copy machine to make more and more 270 00:26:44,330 --> 00:26:49,820 copies of the RNA genome of the virus. The whole cell kind of like foams up and makes 271 00:26:49,820 --> 00:26:56,640 more RNA. And it does so by a copy machine, which is called RNA polymerase, 272 00:26:56,640 --> 00:27:04,950 because RNA is a polymer and a polymerase is an enzyme that's making polymers and an 273 00:27:04,950 --> 00:27:13,850 RNA polymerase is an enzyme that makes more RNA. So one way to block that process 274 00:27:13,850 --> 00:27:18,990 of making more RNAs, which was similarly, you know, stop the infection cycle because 275 00:27:18,990 --> 00:27:24,170 if it can't produce more RNA, it's got nothing to put into new viruses is to use 276 00:27:24,170 --> 00:27:29,230 remdesivir or so we thought for a long time. So does this remdesivir. Remdesivir 277 00:27:29,230 --> 00:27:35,950 looks to the host cell and to RNA polymerase in particular, like a 278 00:27:35,950 --> 00:27:41,710 nucleotide, like a building block for RNA. So basically, things are it's new paper it 279 00:27:41,710 --> 00:27:47,290 can copy on when in reality it's kind of explosive like blocks the entire 280 00:27:47,290 --> 00:27:52,770 polymerase. So you can imagine this like a Trojan horse, remdesivir is the Trojan 281 00:27:52,770 --> 00:27:58,809 horse and RNA dependent RNA polymerase is sure looks like RNA to me and just built 282 00:27:58,809 --> 00:28:05,500 that into the strand. So we'll have a look at this molecule. This is, by the way, I 283 00:28:05,500 --> 00:28:10,240 should probably go back and explain this for a moment. This is what we get out of 284 00:28:10,240 --> 00:28:15,230 our measurements and electron microscopy. So this is the so-called reconstruction 285 00:28:15,230 --> 00:28:18,790 density, and that's what we built a molecule in. So that's like what the 286 00:28:18,790 --> 00:28:23,450 measurement gave us, everything else we have to do by hand. So here is the 287 00:28:23,450 --> 00:28:31,070 density, and this is what the researcher built into it. The template strand, the 288 00:28:31,070 --> 00:28:36,870 old one, which is to be copied, is green, the new one is orange. Remdesivir is 289 00:28:36,870 --> 00:28:43,080 purple and connected to the end, although the program doesn't display it as such. 290 00:28:43,080 --> 00:28:46,880 What you can also see is free magnesium ions. That's their own thing and a de 291 00:28:46,880 --> 00:28:54,110 phosphate. So what are more molecules that researchers modeled in there? Where are 292 00:28:54,110 --> 00:28:58,130 around it as the protein? So I've just quickly depicted it without so you can see 293 00:28:58,130 --> 00:29:01,940 what's happening because it's all very crowded and difficult to see around it as 294 00:29:01,940 --> 00:29:07,330 the protein and a jump of two proteins to copy the RNA and to attach one after the 295 00:29:07,330 --> 00:29:11,960 other, another building block to the bottom of the orange chain. It's gotten a 296 00:29:11,960 --> 00:29:17,149 remdesivir and it tried to put it there and it successfully did. And this 297 00:29:17,149 --> 00:29:22,220 structure was taken as to prove that remdesivir will stop corona. But if you 298 00:29:22,220 --> 00:29:26,110 look at the density, you can see that the free magnesium ions and DIPHOSPHATE has no 299 00:29:26,110 --> 00:29:32,220 density and are not covered by this great cloud, right? So we think they were never 300 00:29:32,220 --> 00:29:39,140 really there. And the remdesivir itself is also not having so much density. So it 301 00:29:39,140 --> 00:29:43,120 turns out that a structure is not quite seeing what the researchers did because 302 00:29:43,120 --> 00:29:48,330 the density doesn't match up with the structure they built. And as we later 303 00:29:48,330 --> 00:29:53,090 found out in clinical trials, is that remdesivir, in fact, doesn't really do 304 00:29:53,090 --> 00:29:58,280 what people hoped, which, among other things, has to do with the fact that RNA 305 00:29:58,280 --> 00:30:03,100 polymerase from corona virus is able to proofread go like, Oh, there's a 306 00:30:03,100 --> 00:30:08,980 remdesivir, then go back free nucleotides take rip out the remdesivir, throw it away 307 00:30:08,980 --> 00:30:15,120 and get the proper nucleotide to build in. So. We're hoping that one over pea-rel will 308 00:30:15,120 --> 00:30:18,839 be better, which, by the way, uses a similar mechanism. It's called a 309 00:30:18,839 --> 00:30:31,870 nucleotide. Yeah, it's similar to a nucleotide. Here's another arrow we found 310 00:30:31,870 --> 00:30:35,070 in the bottom of the structure, only going to show you because I think the software 311 00:30:35,070 --> 00:30:40,150 by Tristan Kroll is so cool, it does a real time molecular dynamics simulation 312 00:30:40,150 --> 00:30:44,510 while you're dragging around your structure. We found that there is an error 313 00:30:44,510 --> 00:30:48,490 in the way the whole molecule was arranged. If there's any specialist, there 314 00:30:48,490 --> 00:30:52,100 was a nine amino acid out of reach associate. OK, I'm going to stop like 315 00:30:52,100 --> 00:30:56,490 geeking out. There was just an error. Let me show you how he correct that. So first 316 00:30:56,490 --> 00:31:00,990 you marks up the wrong region and then he releases it and *quickly flying-away noise* it goes where it's up to 317 00:31:00,990 --> 00:31:04,870 go. I wish my life would always be like this, you said were free days glasses in 318 00:31:04,870 --> 00:31:08,309 front of your computer. You need hours to do this by hand, but his software just 319 00:31:08,309 --> 00:31:15,360 does it. Sorry. It's just if you've spent months doing this, you're totally excited 320 00:31:15,360 --> 00:31:21,580 by this wobbly molecule. I just wanted to show you because I think it's so cool. All 321 00:31:21,580 --> 00:31:29,549 right. Back to a more general content. We have an hour RNA and a let's imagine we 322 00:31:29,549 --> 00:31:35,419 didn't get any like good drugs so far, so the infection cycle is still ongoing. The 323 00:31:35,419 --> 00:31:40,050 RNA now is exported from the endoplasmic reticulum. By the time we make this, we 324 00:31:40,050 --> 00:31:43,750 didn't know how. But Hamburg researchers and Dutch researchers have now found out 325 00:31:43,750 --> 00:31:49,370 how this actually works as a pore here and the pore gets the RNA out. The RNA then 326 00:31:49,370 --> 00:31:53,890 gets packed into new nucleocapsid were also coded by the genome 327 00:31:53,890 --> 00:31:59,760 of the virus, then gets wrapped into a new double membrane, which is host membrane. 328 00:31:59,760 --> 00:32:05,970 Just it has no spikes, which also were produced from the genome. And then, of 329 00:32:05,970 --> 00:32:11,580 course, due the Golgi apparatus is somehow involved, it gets exported. Of course, for 330 00:32:11,580 --> 00:32:17,850 everyone that infected a cell, there will be thousands that are produced and that's 331 00:32:17,850 --> 00:32:26,120 the entirety of the SarsCoV 2 viral life cycle. I know, this was a little bit 332 00:32:26,120 --> 00:32:31,740 much, but I think this is cool and exciting and just about what, you know. I 333 00:32:31,740 --> 00:32:36,980 hope the public can understand about this. It hopefully also tells you why molecular 334 00:32:36,980 --> 00:32:42,740 structures are important, so they let us understand how the virus works, how host 335 00:32:42,740 --> 00:32:48,481 cells are infected. They can help us to find drug targets and to do structure 336 00:32:48,481 --> 00:32:53,370 based drug design, where we find drugs that specifically block these big 337 00:32:53,370 --> 00:32:59,510 molecular machines from doing their work. They also help us to understand the 338 00:32:59,510 --> 00:33:06,549 structures of vaccines and antibodies, and they also let us understand changes due to 339 00:33:06,549 --> 00:33:10,850 two mutations, I haven't got an example because of the time. But when we get a 340 00:33:10,850 --> 00:33:16,010 mutation with the structure, I can kind of tell you, that it is going to change or 341 00:33:16,010 --> 00:33:21,341 that it is going to change only by knowing the new genome. I can already make a 342 00:33:21,341 --> 00:33:25,340 prediction about what the mutation is going to change in a functionality. That's 343 00:33:25,340 --> 00:33:31,850 really important. So in my group, we have some theories what a Micron actually does. 344 00:33:31,850 --> 00:33:36,340 We haven't published and we haven't even tweeted about them yet because we're still 345 00:33:36,340 --> 00:33:43,240 waiting for research results. But it's important to understand these molecular 346 00:33:43,240 --> 00:33:52,169 structures, however, is not very easy to get them. So what are the problems? When we 347 00:33:52,169 --> 00:33:58,750 do our measurement, we get density in this case, the density is blue. It's from the 348 00:33:58,750 --> 00:34:02,179 spike head that I've shown in the beginning, right? So the top that you may 349 00:34:02,179 --> 00:34:06,490 recognize, this looks a little bit like the blue density here. This is the result 350 00:34:06,490 --> 00:34:10,919 from our research. And in this case, I have built almost all of the molecule 351 00:34:10,919 --> 00:34:15,290 already, so I'm going to show it. This is like the software. We're actually using a 352 00:34:15,290 --> 00:34:19,659 tenfold to speed I'm usually using, and I would usually be sitting there with 3D 353 00:34:19,659 --> 00:34:24,190 glasses. So here's the density. I said that with my 3D glasses and this bit 354 00:34:24,190 --> 00:34:30,579 hasn't been built, so you can now see me like by hand. And one bit of molecule 355 00:34:30,579 --> 00:34:34,999 after the other trying to get the murder ought to be, and you can quite well see 356 00:34:34,999 --> 00:34:40,030 that the computer is not able to do it all automatically. So I have to help it a 357 00:34:40,030 --> 00:34:44,240 little bit. And as I said, it's about 10 times the speed. It's even got like the 358 00:34:44,240 --> 00:34:49,179 warning from the bin program not reacting all of the software, it's also not 359 00:34:49,179 --> 00:34:53,800 commercial. This has been developed by other scientists, so the usability is like 360 00:34:53,800 --> 00:34:59,609 so-so cool, just an amazing program. But if you want some new functionality, you 361 00:34:59,609 --> 00:35:04,440 better program it yourself, because perhaps no one else is going to do it. And we have 362 00:35:04,440 --> 00:35:10,549 actually contributed with a plug in or two to cut. Yeah, you can see it's not always 363 00:35:10,549 --> 00:35:13,869 easy, so I try and go, like, now it's good. Settings should nicely in the 364 00:35:13,869 --> 00:35:21,890 density and here it's fairly easy. My students love doing this is like for them. 365 00:35:21,890 --> 00:35:25,099 It's like computer gaming. They do it for three months straight. If you don't like, 366 00:35:25,099 --> 00:35:30,450 get them off the chair, go right up your physics. They'll do it forever. And 367 00:35:30,450 --> 00:35:35,289 secretly, I'm jealous. Because I also like doing this. I don't know if you can 368 00:35:35,289 --> 00:35:45,499 follow, but this is like playing a game. Away, if you're interested in playing this 369 00:35:45,499 --> 00:35:54,010 game, we are also having. Like practical places and stuff. Right! So building, 370 00:35:54,010 --> 00:35:58,790 building, building, going like, oh, there's another alanine, I need a pralines 371 00:35:58,790 --> 00:36:03,609 or mutated it. I go like, Yeah, OK, now it's all nicely sitting. So that was easy. 372 00:36:03,609 --> 00:36:09,240 But what do I do here? So I've built for something here. But is it correct? The 373 00:36:09,240 --> 00:36:12,950 density does not really tell me what's going on here, and I'm going to show it 374 00:36:12,950 --> 00:36:18,680 this to you in slower again. So you understand the problem, right? In this 375 00:36:18,680 --> 00:36:22,720 then part of the density, I can really not tell only from the density what's going 376 00:36:22,720 --> 00:36:28,890 on. I know approximately what a molecule must look like due to the sequence. So 377 00:36:28,890 --> 00:36:31,740 I've got some information. I know which Atom is connected to which, but how it all 378 00:36:31,740 --> 00:36:37,119 three dimensionally fits in here, even if I know which lines have to go in, there is 379 00:36:37,119 --> 00:36:41,849 super hard. So it would be very easy for me to make an error here, because the 380 00:36:41,849 --> 00:36:45,979 measurement data don't tell me enough about what the model actually should look 381 00:36:45,979 --> 00:36:55,500 like and several interpretation., everal models would all be possible. So this is 382 00:36:55,500 --> 00:36:59,130 kind of difficult. I'm just seeing a questionnaire that I may want to answer 383 00:36:59,130 --> 00:37:03,670 right away. Within could is it possible to verify if you have chosen created the 384 00:37:03,670 --> 00:37:09,379 right building blocks, you know, the building blocks because of the genome? So 385 00:37:09,379 --> 00:37:14,539 Gene tells you the order of amino acids you want to put after each other. So if 386 00:37:14,539 --> 00:37:21,839 you started at the right point, the rest will also be like the correct atoms and 387 00:37:21,839 --> 00:37:26,039 the correct connection. But how it like three dimensionally faults, you don't 388 00:37:26,039 --> 00:37:36,600 know. You have to make that on the density. So it is possible to do it. You 389 00:37:36,600 --> 00:37:41,910 have to write building blocks at hand. Usually if there are if there is like, you 390 00:37:41,910 --> 00:37:46,160 know, if a magnesium ion, for example, is sitting there, the magnesium ion was not 391 00:37:46,160 --> 00:37:51,250 in your genomic information. You just need to know what you're doing to recognize 392 00:37:51,250 --> 00:37:58,190 this is a magnesium ion ore does this a diophosphate or something like this? 393 00:37:58,190 --> 00:38:06,490 Right. Going to answer the rest of the questions later. Molecular models need to 394 00:38:06,490 --> 00:38:11,049 be built by hand. This can lead to errors. There a few automatic algorithms do work 395 00:38:11,049 --> 00:38:17,059 under favorable circumstances, but most of the stuff still has to happen by hand. As 396 00:38:17,059 --> 00:38:21,549 of today, and I got my postdoc from like holidays for 15 minutes today, and he gave 397 00:38:21,549 --> 00:38:25,500 new numbers. So we've got 1909 molecular structures 398 00:38:25,500 --> 00:38:31,729 today. New structures come out every Wednesday. There are 1334 from X-ray 399 00:38:31,729 --> 00:38:36,109 crystallography. That's the thing. With the particle accelerator in Hamburg, I 400 00:38:36,109 --> 00:38:41,150 thought, they have been measured at synchrotrons all over the world. Not only 401 00:38:41,150 --> 00:38:46,079 Hamburg, where BioNTech structures have been measured, but also had SARS. There 402 00:38:46,079 --> 00:38:51,890 have been large screens a diamond in Japan and China at Sesamia, at Solemy, in 403 00:38:51,890 --> 00:38:57,349 America. Synchrotrons all over the world contributed to this. 35 from nuclear 404 00:38:57,349 --> 00:39:02,470 magnetic resonance, which is a little bit of a niche method for this type of study. 405 00:39:02,470 --> 00:39:08,579 And 566 from electron microscopy. So 1909 molecular structures 406 00:39:08,579 --> 00:39:16,339 of different states of 17 macromolecules, 17 proteins from a total 407 00:39:16,339 --> 00:39:26,789 of 28. So corona virus in total has 28 different genes, 4 proteins. There are 28 408 00:39:26,789 --> 00:39:33,079 proteins. And we only structurally know 17 of them. And then we have like different 409 00:39:33,079 --> 00:39:37,119 versions of them, different ph, different temperatures, spike, head bit of spike 410 00:39:37,119 --> 00:39:47,259 head, spike head with antibody, things like that. So a 1900 data sets that's in total. 411 00:39:47,259 --> 00:39:51,980 Errors and structures, as we've just seen, can happen because fit between 412 00:39:51,980 --> 00:39:58,940 the data and model is bad, because complete automation is not possible. Models are 413 00:39:58,940 --> 00:40:04,819 built manually expertize in many different areas needed. You need to be good 414 00:40:04,819 --> 00:40:07,819 software. You need to have done all the lab work. The measurement needs to be done 415 00:40:07,819 --> 00:40:12,269 right. Processing needs to be made. You need to know your statistical validation. 416 00:40:12,269 --> 00:40:17,180 You need to know your chemistry. You need to know your biology. So it's really not 417 00:40:17,180 --> 00:40:22,230 easy and you need to know your 3D goggles unless you get sick from them, in which 418 00:40:22,230 --> 00:40:27,720 case you can't use them. One of the major aspects of software, the methods you're 419 00:40:27,720 --> 00:40:35,789 using and this is where we come in. Small structural errors can lead to big 420 00:40:35,789 --> 00:40:41,000 structural problems downstream. Imagine the bid was to remdesivir, the diphosphate 421 00:40:41,000 --> 00:40:45,979 there, the fact that there was something bound into that structure that was not 422 00:40:45,979 --> 00:40:51,769 really there. But the model had dose like additional free magnesium ions down the 423 00:40:51,769 --> 00:40:59,809 line, as I know from insiders, led to like waste of hundreds thousands of dollars 424 00:40:59,809 --> 00:41:05,299 and many hours of work time in drug discovery because they kind of like fed 425 00:41:05,299 --> 00:41:09,990 this model in order to find a drug that ultimately never bound because of 426 00:41:09,990 --> 00:41:17,680 magnesium ion wasn't actually there. So if we make small structures, that builds 427 00:41:17,680 --> 00:41:21,599 up hugely for the downstream applications where they need these molecular 428 00:41:21,599 --> 00:41:31,279 structures. Errors are common. And now we add to this an ongoing pandemic. Right. 429 00:41:31,279 --> 00:41:35,720 And her scientists are there to rescue today. Lockdown happened, you're sitting 430 00:41:35,720 --> 00:41:41,339 at home, there are no colleagues to help you. Your child is home schooling. The dog 431 00:41:41,339 --> 00:41:45,430 wants to be fed, your grandma calls, because she's worried and you've got to 432 00:41:45,430 --> 00:41:50,939 solve the spike structure on which lives will depend as fast as possible. Normally, 433 00:41:50,939 --> 00:41:54,450 we take a year to five to solve a structure, and in the pandemic you only 434 00:41:54,450 --> 00:42:03,940 got three months. Of course, errors are going to happen. So that's well, just a 435 00:42:03,940 --> 00:42:08,779 matter of fact. We've got to arrange ourselves with it. It's not the fault of 436 00:42:08,779 --> 00:42:14,170 individuals, it's how the whole thing works. It's such a complex process. Errors 437 00:42:14,170 --> 00:42:19,539 are going to happen! Now in normal life my team and I methods developers and 438 00:42:19,539 --> 00:42:24,589 structural biology. We are the people, who give us the experimental techniques and 439 00:42:24,589 --> 00:42:30,670 software to solve their structures as best as we and they can. We're not usually in 440 00:42:30,670 --> 00:42:36,569 the in the stage like we're usually, you know. For every Nobel Prize, there have 441 00:42:36,569 --> 00:42:41,109 been like dozens of Nobel Prizes in structural biology has been methods 442 00:42:41,109 --> 00:42:45,059 developed in the background to develop the methods that made it possible to see, you 443 00:42:45,059 --> 00:42:49,299 know, the structure of the DNA double helix or structure of the ribosome, or the 444 00:42:49,299 --> 00:42:56,029 structure of the influenza virus. It's just that normally we're just enablers. 445 00:42:56,029 --> 00:43:05,130 However, here was the pandemic and very many structures that had errors. So we did 446 00:43:05,130 --> 00:43:10,509 what we needed to do. We came together as a relatively large team under my 447 00:43:10,509 --> 00:43:17,279 leadership, we are today 23 people, we peaked at 27 last year from nine countries 448 00:43:17,279 --> 00:43:21,009 to check an improve the molecular structures of SARS-CoV-1 and SARS-CoV-2. 449 00:43:21,009 --> 00:43:31,369 So. We are methods developers, most of are methods developers, we are specialists in 450 00:43:31,369 --> 00:43:36,441 solving structures. We evaluate all the published Structures and Protein Data 451 00:43:36,441 --> 00:43:43,619 Databank or PDB from SARS and SARS- CoV-2. We reprocess all of them and we 452 00:43:43,619 --> 00:43:49,549 remodel them, although not all are looked at manually, because that would be just 453 00:43:49,549 --> 00:43:53,309 too much. We also do a scientific dissemination, putting these structures 454 00:43:53,309 --> 00:43:58,430 into context for people who want to start doing molecular research on corona virus. 455 00:43:58,430 --> 00:44:04,680 And we do public outreach. I'll give you a quick insight into our pipeline because I 456 00:44:04,680 --> 00:44:10,039 thought the software might be interesting for you. So every Wednesday come new 457 00:44:10,039 --> 00:44:14,529 entries of molecules in the protein databank, which is, by the way, the World 458 00:44:14,529 --> 00:44:19,039 Wide Protein Databank is an open, open resource. Everyone in the world can 459 00:44:19,039 --> 00:44:23,470 download the new structures, and all the journals require people who make new 460 00:44:23,470 --> 00:44:28,099 structures to put them there, which is nice. I'm really privileged to be in a 461 00:44:28,099 --> 00:44:33,150 field where the data are public. We compared the new structures with the NCBI 462 00:44:33,150 --> 00:44:37,950 proteomics, so the genes from corona virus to find the structures that belong to 463 00:44:37,950 --> 00:44:44,109 corona virus, put everything into an sql metha database. Then we calculate how 464 00:44:44,109 --> 00:44:48,529 different the structures are from the ones we already know. We look whether all 465 00:44:48,529 --> 00:44:52,480 measurement data available, so we have a big problem of not all measurement data 466 00:44:52,480 --> 00:44:58,640 being published. I hope we are going to be like astronomy one day, where everything 467 00:44:58,640 --> 00:45:06,440 gets published. I am sitting in the some German cometies to that end STIKO AM which 468 00:45:06,440 --> 00:45:11,059 is a very new hub. And then we run a number of specialized programs which all 469 00:45:11,059 --> 00:45:16,349 do validation and put the results on GitHub immediately. On Thursday, at the 470 00:45:16,349 --> 00:45:22,160 latest, researchers can find our elevation, remodeling and the quality indication for 471 00:45:22,160 --> 00:45:28,770 the structure everything, that can be done automatically online. We then, for some 472 00:45:28,770 --> 00:45:33,970 structures, manually rebuilt them, so we actively look weathered our problems, that 473 00:45:33,970 --> 00:45:38,200 was, for example, the case with the remdesivir structure. We tried to do this 474 00:45:38,200 --> 00:45:42,500 for those structures that we think drug designers will use the most or that are 475 00:45:42,500 --> 00:45:47,910 really important. And when we find errors, we contact our original office first and 476 00:45:47,910 --> 00:45:55,119 tell them we found an error here is the corrected structure. Use our data, you 477 00:45:55,119 --> 00:46:00,929 don't need to cite us, just correct your structure in the database, please. This 478 00:46:00,929 --> 00:46:05,269 means we won't get credit, but I meant that at the beginning of the pandemic, 479 00:46:05,269 --> 00:46:11,279 people were adjusting their structures already when the preprint was out, so 480 00:46:11,279 --> 00:46:15,420 there would not be problems downstream. And I have often been asked I would like 481 00:46:15,420 --> 00:46:20,789 to like this again. That was really like why people accepted our corrections, 482 00:46:20,789 --> 00:46:25,539 because they didn't need to give anyone credit. They could just like change them. 483 00:46:25,539 --> 00:46:30,230 And the database is also online, so everyone from the Philippines to the U.S. 484 00:46:30,230 --> 00:46:34,940 can just use them, whether it's like a commercial person or a taxpayer, or a 485 00:46:34,940 --> 00:46:40,559 private person research institution, a foundation, everyone can use our data. 486 00:46:40,559 --> 00:46:44,309 They're just online there for everyone, and we only ask them to give us credit in 487 00:46:44,309 --> 00:46:51,109 the form of a reference citation. We disseminate the data via GitHub via 488 00:46:51,109 --> 00:46:57,190 Twitter. 3D bio notes, which is a three dimensional database linking directly into 489 00:46:57,190 --> 00:47:06,640 our database, we contact the offers. We also have entries in Proteopedia. Molprobity, 490 00:47:06,640 --> 00:47:11,450 which is a virtual bioinformatics institute, links directly into our 491 00:47:11,450 --> 00:47:15,100 database. So they're always like up to date showing what we are doing. We have a 492 00:47:15,100 --> 00:47:20,440 homepage and we do reviews. There's a lot of downstream users. The biggest ones are 493 00:47:20,440 --> 00:47:29,309 the EU Jedi Grand Challenge folding at home, which peaked out in July last year. 494 00:47:29,309 --> 00:47:36,809 I think a 2.4 xTFLOPs computing power for molecular simulations and used in the 495 00:47:36,809 --> 00:47:43,830 majority our models to start from. And also very big is IBM open pandemics. But 496 00:47:43,830 --> 00:47:47,989 there are a number of others, plus many individual apps. So we found a great new 497 00:47:47,989 --> 00:47:55,469 many friends. Here is our homepage, that's where you can find it. There's also an 498 00:47:55,469 --> 00:48:01,489 English version, you can find blog posts for the public and for scientists. And in 499 00:48:01,489 --> 00:48:07,020 the end, I would like to talk for like five minutes about daily life in ritual 500 00:48:07,020 --> 00:48:14,529 mobility. So my team is over 20 people from nine to ... we cover nine time zones, 501 00:48:14,529 --> 00:48:21,520 right? Where nine hours time shift apart. And we had several lockdowns. So. 502 00:48:21,520 --> 00:48:26,839 Actually, the majority of people in the task force, about half of them don't work 503 00:48:26,839 --> 00:48:31,580 for me. They are volunteering their researchers elsewhere that volunteer to be 504 00:48:31,580 --> 00:48:36,349 a part of this effort. And there are many people in the task force who have never 505 00:48:36,349 --> 00:48:43,989 like personally met. So how do you make group coherence if you are working for 20 506 00:48:43,989 --> 00:48:49,450 months or 22 months by now in an environment like this, right? We founded 507 00:48:49,450 --> 00:48:56,020 ourselves in March 2020 as a chat group called the Coronavirus Structural Task 508 00:48:56,020 --> 00:49:02,839 Force, which was a job back then. It didn't remain a joke. But that's how life 509 00:49:02,839 --> 00:49:08,400 plays. We have everyday Zoom meetings at 10 o'clock, one time per week in the 510 00:49:08,400 --> 00:49:14,700 afternoon. So do people from Oregon can join us. We do a lot of like media 511 00:49:14,700 --> 00:49:20,440 outreach in international and German media. We've been like on nano and Terra X 512 00:49:20,440 --> 00:49:24,599 and Planet E, we've been in breakfast television. That was a particularly 513 00:49:24,599 --> 00:49:30,069 interesting experience. My email got link to Querdenker and I got a few very 514 00:49:30,069 --> 00:49:34,579 interesting email exchanges. I also must say I never got insulted or frightened by 515 00:49:34,579 --> 00:49:41,589 anyone, so I just discussed with them and it worked out. And I'm happy because like 516 00:49:41,589 --> 00:49:49,410 I understood, like how, what the theories are, and that was very interesting. Keep 517 00:49:49,410 --> 00:49:53,680 the media also like to write about my hair, my eyes, blah blah blah on these 518 00:49:53,680 --> 00:49:58,440 things. I just want to note that Streeck is about my age, and Drosten is only nine 519 00:49:58,440 --> 00:50:05,980 years older than me. So really? OK, whatever. Most importantly, they're 520 00:50:05,980 --> 00:50:11,300 talking about our research. We also did a lot of social media. I got a Twitter 521 00:50:11,300 --> 00:50:15,880 account. Everyone else did as well. You can watch us work on Twitch if you're 522 00:50:15,880 --> 00:50:18,930 interested. We found that people find it soothing to see us modeling these 523 00:50:18,930 --> 00:50:23,519 structures. I was requested to make stickers for the team as soon as we got a 524 00:50:23,519 --> 00:50:28,719 grant and we got funded by the Federal Ministry for Research and Education in 525 00:50:28,719 --> 00:50:34,130 2020. We have a YouTube channel where you can, for example, see the entry animation 526 00:50:34,130 --> 00:50:40,510 and the students brought a cactus, which is called Corina the Corona Cactus. I 527 00:50:40,510 --> 00:50:47,470 know. It looked like we had fun, and we did. I can tell you being caught, you 528 00:50:47,470 --> 00:50:55,119 know, being at home, having to care for your children. Having people dying. Having 529 00:50:55,119 --> 00:50:59,880 an ongoing pandemic, knowing that I 'd be more open pandemics is going to spend 530 00:50:59,880 --> 00:51:04,589 another million based on your research. And also that ZDF wants to talk to you and 531 00:51:04,589 --> 00:51:09,981 the Berliner Abendblatt. This is so stressful! Think about all the 532 00:51:09,981 --> 00:51:15,349 responsibility we had, and it was really terrible for us, so we needed to cheer up 533 00:51:15,349 --> 00:51:19,999 every here and then, the whole group kind of like grew together and we all became 534 00:51:19,999 --> 00:51:25,999 friends. This was unheard. For us, it was very uncommon as researchers. Typically, 535 00:51:25,999 --> 00:51:29,029 our behavior with each other is much more formal than their behavior and this group 536 00:51:29,029 --> 00:51:35,880 was. But these were like exceptional times, and we wanted to fight the pandemic 537 00:51:35,880 --> 00:51:40,640 and inform the public. That's what we were there for and was not so much about 538 00:51:40,640 --> 00:51:49,340 personal gain. And that was nice. We have a group chat. You know, I mean, I'm 539 00:51:49,340 --> 00:51:53,289 talking to right audience, right? We have a group chat. Do you know what that looks 540 00:51:53,289 --> 00:51:57,759 like? Let me tell you. Typically, professors don't communicate with this. 541 00:51:57,759 --> 00:52:05,869 We have a virtual, Oh, we have a virtual space. We hope to change to work 542 00:52:05,869 --> 00:52:13,130 adventure soon. We all want to play games in the evening occasionally with the 543 00:52:13,130 --> 00:52:17,960 group, so we do some team building efforts. When people can meet in person, 544 00:52:17,960 --> 00:52:22,540 they usually do and sometimes they go and travel and like, meet each other. But this 545 00:52:22,540 --> 00:52:31,079 has been very limited. And we did grow together as a network, that will be there 546 00:52:31,079 --> 00:52:37,390 after the pandemic, so we are 25 people all over the planet that did this 547 00:52:37,390 --> 00:52:43,980 together. And even if we wouldn't have made any difference against the virus, I 548 00:52:43,980 --> 00:52:49,890 would still be happy to have done it for the friendships I made. However, we did 549 00:52:49,890 --> 00:52:54,910 make a dent. We don't quite know how big it is because our science was open science 550 00:52:54,910 --> 00:53:00,509 and the results could be gotten by everyone without reference. But we know a 551 00:53:00,509 --> 00:53:07,700 few things wouldn't have happened without us. And I'm. Deeply grateful for having 552 00:53:07,700 --> 00:53:17,739 had a purpose during this pandemic. In the end, I have a little bit of a more serious 553 00:53:17,739 --> 00:53:27,099 topic. My contract is going to run out in May. I think it's going to be prolonged. 554 00:53:27,099 --> 00:53:35,630 When it will, I'll be signing my 14 work contract since 2008. 14, like I had 13 555 00:53:35,630 --> 00:53:43,619 year contracts already out of all my task force members, there is only one holding a 556 00:53:43,619 --> 00:53:50,849 permanent position and two which are retired. Everyone else, including six 557 00:53:50,849 --> 00:53:56,990 people whose contract is going to run out next year, are on temporary contracts and 558 00:53:56,990 --> 00:54:02,140 not students. Students are extra. That the students are on time limited contracts is 559 00:54:02,140 --> 00:54:08,380 OK, but Germany's got a problem. 84 percent of academics in German 560 00:54:08,380 --> 00:54:17,529 universities are on time limited contracts. So are we. Only one task force 561 00:54:17,529 --> 00:54:22,779 member has was a permanent position signed, and that's not me. And this is not 562 00:54:22,779 --> 00:54:27,440 so much on my behalf, because I'm going to find my way through life. Look at all the 563 00:54:27,440 --> 00:54:32,380 exposure I had, but there are people out there who are single moms and dads, who 564 00:54:32,380 --> 00:54:36,769 come from less privileged backgrounds or had a harder life and who can just not 565 00:54:36,769 --> 00:54:44,740 afford to be on one year contracts all the time while holding a Ph.D.. We're losing 566 00:54:44,740 --> 00:54:48,920 all these bright people and I'm seeing them right. They leave my institute and 567 00:54:48,920 --> 00:54:52,759 they go to industry. And then the universities complain that they're not 568 00:54:52,759 --> 00:55:00,700 competitive. We need to change the system. We need to have more permanent positions 569 00:55:00,700 --> 00:55:07,309 in science. I promise we won't perform worse, if you give us permanent contracts. 570 00:55:07,309 --> 00:55:16,989 We love what we are doing. So back to the corona topic. In order to understand the 571 00:55:16,989 --> 00:55:22,029 virus and its life cycle, we need to understand its molecular biology. This 572 00:55:22,029 --> 00:55:27,759 will help with the design of therapeutics. We evaluated these molecular structures 573 00:55:27,759 --> 00:55:32,869 with a bespoke pipeline, an expert knowledge provided context and reached out 574 00:55:32,869 --> 00:55:37,969 to the taxpayer and the general public to inform them. We also wrote a paper 575 00:55:37,969 --> 00:55:43,400 together with long off a list making the invisible enemy visible, which is our 576 00:55:43,400 --> 00:55:49,129 motto. And as we started this all with questions, I'm going to end with 577 00:55:49,129 --> 00:55:55,239 questions. Structural biology remains difficult. What can we learn from our 578 00:55:55,239 --> 00:56:01,499 findings? Should we, as a scientists community, change our attitudes towards 579 00:56:01,499 --> 00:56:10,640 errors? Should this serve as a model for other projects, cannot serve as a model 580 00:56:10,640 --> 00:56:14,400 for other projects? I hadn't thought about this, but a nature editor asked me when I 581 00:56:14,400 --> 00:56:18,809 was writing a comment whether we believe that science should always be like this? 582 00:56:18,809 --> 00:56:23,459 My God, that would be awesome. I would totally be up for it if science would 583 00:56:23,459 --> 00:56:27,009 always be like this! Come together with a bunch of friends, but without funding! 584 00:56:27,009 --> 00:56:32,210 Start doing something to, you know, fight a global pandemic, then get some funding. 585 00:56:32,210 --> 00:56:39,489 Still, having like no senior people on a project. Can open science compete? I don't 586 00:56:39,489 --> 00:56:49,099 know. We get pretty little credit. It would, definitely. OK, science compete. I 587 00:56:49,099 --> 00:56:53,289 don't know, it doesn't quite look like it still getting measured only by the 588 00:56:53,289 --> 00:56:58,979 citations my paper gets. And well, at least a paper is not behind a paywall, but 589 00:56:58,979 --> 00:57:02,799 if we would have published all our stuff in like papers would possibly get more 590 00:57:02,799 --> 00:57:09,369 credit. I really don't know, but we need to work on this. If we want science, we 591 00:57:09,369 --> 00:57:16,700 need to change how people are rewarded. How senior they really need to be. I'm 39. 592 00:57:16,700 --> 00:57:22,200 It seems I'm called a junior group leader. All of us are young. The youngest is 24. 593 00:57:22,200 --> 00:57:26,859 He's writing our first Alpha article about a corona virus protein. I feel that the 594 00:57:26,859 --> 00:57:31,259 German academic system and all over the world, actually you need to be older and 595 00:57:31,259 --> 00:57:37,119 older to become a professor and be permanent and be like a grant holder. I 596 00:57:37,119 --> 00:57:41,180 don't think it's necessary, I think that professors could be 30 and the world 597 00:57:41,180 --> 00:57:49,030 wouldn't, you know, like, go down. Well, what will change in science after a 598 00:57:49,030 --> 00:57:54,289 pandemic? We had like large exposure. It certainly will also have to do with like 599 00:57:54,289 --> 00:57:58,580 questions like did the virus now come from an app or didn't it? That, you know, would 600 00:57:58,580 --> 00:58:03,720 change how people view science, I'm sure. How will scientists be viewed by the 601 00:58:03,720 --> 00:58:08,960 public? Right. Right now, of course, you know, mom and dad are very proud, but. 602 00:58:08,960 --> 00:58:14,119 What's going to change? Are we going to still be the bad guys because we often 603 00:58:14,119 --> 00:58:19,180 are. But I'm like general, exclusively taxpayer funded. I never took any money 604 00:58:19,180 --> 00:58:23,519 from the pharmaceutical industry. I have like, you know, no stakes in this game. 605 00:58:23,519 --> 00:58:31,959 I'm just like earning tax money, so I feel that, there is a whole complex of 606 00:58:31,959 --> 00:58:35,420 difficult things there, how people regard science, but definitely the pandemic is 607 00:58:35,420 --> 00:58:40,079 going to change, how science is going to be viewed. What's that going to be? 608 00:58:40,079 --> 00:58:48,400 *Exspiration* In the end. I'd like to thank all the task force members and all 609 00:58:48,400 --> 00:58:54,000 our collaboration partners and our scientific fairy godmother, Alvin Pearson, 610 00:58:54,000 --> 00:58:59,099 who had little role in this research but much role in our mentorship and bringing 611 00:58:59,099 --> 00:59:04,299 us forward. My home, the University of Hamburg, the Coronavirus Structural 612 00:59:04,299 --> 00:59:08,499 Taskforce, our we are funded by the Deutsches Officials Command Trust and the 613 00:59:08,499 --> 00:59:13,699 Federal Ministry for Research and Education. I would like to point out that 614 00:59:13,699 --> 00:59:19,130 we are looking for student assistance, not only for scientific work, but also for 615 00:59:19,130 --> 00:59:25,430 social media video and programing work and 3D printing. So if you know anyone who's 616 00:59:25,430 --> 00:59:30,710 interested, please point him in my direction. My email is there. We are also 617 00:59:30,710 --> 00:59:36,219 offering Bachelor, Master and Ph.D. thesis in areas that cover both Lab work and 618 00:59:36,219 --> 00:59:43,691 computer work, which is a rare thing these days. You can find us on YouTube and the 619 00:59:43,691 --> 00:59:50,990 internet and on Twitter and. I'm looking forward to the discussion. And thanks for 620 00:59:50,990 --> 00:59:53,549 listening. melzai_a: You write it, so.*laughing* 621 00:59:53,549 --> 00:59:57,660 Andrea: I just brought it up, must have bmbF because I'm now sitting on the screen 622 00:59:57,660 --> 01:00:01,519 on dislike committees more and more, I'm reaching an age where I'm sitting on 623 01:00:01,519 --> 01:00:05,359 committees and I told them legacy software is a problem. 624 01:00:05,359 --> 01:00:07,900 melzai_a: It's a real.big problem. Andrea: You know, it's very troubling that 625 01:00:07,900 --> 01:00:12,829 the software is written in Fortran. Not every second Linus go to, so it's written 626 01:00:12,829 --> 01:00:17,930 like assembler. No one knows what's in there anymore. And if a person dies, we're 627 01:00:17,930 --> 01:00:21,530 not going to be able to do anything about the algorithms. They're just going to be 628 01:00:21,530 --> 01:00:24,810 lost. melzai_a: Exactly. And they are. So you 629 01:00:24,810 --> 01:00:28,459 have to first influence to grant writing institutes that there are grants out so 630 01:00:28,459 --> 01:00:32,849 that this software can read is reversed. And this software is not easy. So that's 631 01:00:32,849 --> 01:00:36,650 not your typical web page, so you need to work together in such groups. And so it's 632 01:00:36,650 --> 01:00:41,720 a very interesting piece of the problem, I have to say. So sadly, as a PhD student went, 633 01:00:41,720 --> 01:00:45,629 we weren't we were looking into this for the second. Ah.. This is too big of a cake 634 01:00:45,629 --> 01:00:49,990 to eat. *laughing* It was very interesting. So I can also this and you 635 01:00:49,990 --> 01:00:53,630 let you do it. The nudel tool suite, and that's also only maintained by, I think, 636 01:00:53,630 --> 01:01:00,739 three people also. So even that one, it's with many more. It's still not good. So 637 01:01:00,739 --> 01:01:05,900 just my sense of that one. Andrea: So I brought my Ph.D. thesis. I 638 01:01:05,900 --> 01:01:08,329 worked on chalex?? and that faces similar problems. 639 01:01:08,329 --> 01:01:15,319 melzai_a: Yeah, it's it's just used in the entire world to solve every small molecule 640 01:01:15,319 --> 01:01:20,359 structure. There is more or less it was like, Yeah, so questions were the 641 01:01:20,359 --> 01:01:25,440 questions. Frankly, we ain't got a first question, I think around 20 or 30 minutes 642 01:01:25,440 --> 01:01:30,269 ago, if we yeah, that's that's why that was so great as a signal angel, she's 643 01:01:30,269 --> 01:01:34,969 picking up all of these points. And so the first question was how do the virus 644 01:01:34,969 --> 01:01:37,400 variants affect the shape or form of the virus? 645 01:01:37,400 --> 01:01:44,329 Andrea: I think they so no matter like, OK, this is the old model as we know, then 646 01:01:44,329 --> 01:01:48,690 there should be fewer spikes and should be a bit smaller. But nothing would change on 647 01:01:48,690 --> 01:01:54,920 this view, like the scale is way too large. The mutations each change about 10 648 01:01:54,920 --> 01:02:01,099 atoms, so every like amino acid at this different, it's about 10 atoms. And those 649 01:02:01,099 --> 01:02:06,420 changes would be so small you could not see them on the virus model. You'd 650 01:02:06,420 --> 01:02:10,239 actually need to look at the head of the spike in order to see the mutation and 651 01:02:10,239 --> 01:02:16,079 what it actually does. So the changes are too small to show them in the model. That 652 01:02:16,079 --> 01:02:20,499 doesn't mean they're not meaningful. So as you've seen, like the head of the spike 653 01:02:20,499 --> 01:02:28,079 binds to the host, to the host cell, to ACE2 receptor, and that binding is highly 654 01:02:28,079 --> 01:02:35,920 influenced by this by the mutations. Now we found that we may end up lucky because 655 01:02:35,920 --> 01:02:41,729 the same paths were to antibody as binding is also the piece that binds to the host 656 01:02:41,729 --> 01:02:47,380 cell. So everything that would mate despite change in a way that the antibody 657 01:02:47,380 --> 01:02:55,170 couldn't bind any more to it. For its head would have also changed how it bound to 658 01:02:55,170 --> 01:03:03,000 the host cell. However, it seems that Omicron is still able to bind human cells 659 01:03:03,000 --> 01:03:08,780 very efficiently, while antibodies cannot recognize it so easily. That may have to 660 01:03:08,780 --> 01:03:13,099 do with like this finger's actually like packed and you could imagine like putting 661 01:03:13,099 --> 01:03:17,999 cotton wool around it. That's called glycosylation. It's got long sugar changes 662 01:03:17,999 --> 01:03:22,840 that are rule, and they're there to obscure the immune system, like the 663 01:03:22,840 --> 01:03:27,530 antibody goes like orders, wool. I can't really find where I'm on to bind. Is it 664 01:03:27,530 --> 01:03:34,210 here? I don't know. And that's changed in Omicron, but it's not fully understand 665 01:03:34,210 --> 01:03:40,519 yet. I saw there was a new structure this week, but I haven't looked at it yet. 666 01:03:40,519 --> 01:03:44,529 However, the changes are too small to show it in the virus model. They're like really 667 01:03:44,529 --> 01:03:50,819 tiny changes. And another change that happens in Omicron as well is the 668 01:03:50,819 --> 01:03:56,799 proofreading mechanism. When the RNA is copied is like damaged and we think it's 669 01:03:56,799 --> 01:04:01,869 damaged. So their so-called eNd RNA, which is a proofreading protein, its sharp is 670 01:04:01,869 --> 01:04:06,630 like to go like a star and correct? Yes, correct, correct. Correct. That seems to 671 01:04:06,630 --> 01:04:10,959 be a little bit broken. So it could be that Omicron is accumulating so many 672 01:04:10,959 --> 01:04:17,229 mutations because it's RNA copy machine. It's like not working as it should is 673 01:04:17,229 --> 01:04:21,630 basically not proofreading. That would mean that more viruses are produced that 674 01:04:21,630 --> 01:04:26,549 are not viable and cannot survive. But it would also mean that it mutates much 675 01:04:26,549 --> 01:04:32,009 faster, and we think that may have an influence. But that's just theory. So far 676 01:04:32,009 --> 01:04:36,799 this hypothesis, we haven't proven it yet. So this is why I haven't tweeted about it 677 01:04:36,799 --> 01:04:42,059 yet, because it's just a theory, but it would make sense, right? 678 01:04:42,059 --> 01:04:46,400 melzai_a: Connected to that, I would have a question the ice receptor of small children 679 01:04:46,400 --> 01:04:51,339 is a little bit different than that one of the adults to you do know about that 680 01:04:51,339 --> 01:04:56,049 because all the concern to what's more, the smaller children are the defense. 681 01:04:56,049 --> 01:05:01,499 Andrea: I can't. I have read that, but I haven't looked into it properly. So I'm 682 01:05:01,499 --> 01:05:06,249 I'm afraid I'm not going to answer this question because I feel I would rather not 683 01:05:06,249 --> 01:05:08,319 say anything about it than say something that's wrong especially. 684 01:05:08,319 --> 01:05:11,839 melzai_a: Well. We're looking forward to the secretary's right in the public PDB so 685 01:05:11,839 --> 01:05:19,099 that everybody can look at them and. Andrea: Know we live in an age of 686 01:05:19,099 --> 01:05:23,079 preprint, and very often the PDB papers are there when a preprint comes out, which 687 01:05:23,079 --> 01:05:28,079 is how we called so many errors, right? They published a preprint, they put out a 688 01:05:28,079 --> 01:05:32,349 structure. We went like, there's errors in the structures. And then when they 689 01:05:32,349 --> 01:05:34,880 published actual paper, everything was corrected. 690 01:05:34,880 --> 01:05:39,380 melzai_a: And she's agreed that believe the changes, I think are checked on the 691 01:05:39,380 --> 01:05:42,619 PDB. melzai_a: This is, in fact, because yes, 692 01:05:42,619 --> 01:05:45,799 that's that's what IT people like because then that, you know, there's a 693 01:05:45,799 --> 01:05:52,079 history is very important. And there's a second question and it goes towards the 694 01:05:52,079 --> 01:05:54,119 tools that I use to simulate those molecules. 695 01:05:54,119 --> 01:05:59,359 Andrea: Wait, wait, wait, wait. I have a follow up to this: thing that I would 696 01:05:59,359 --> 01:06:03,890 really like to see, but it hasn't happened yet. The PDB is a very static repository 697 01:06:03,890 --> 01:06:09,229 where only original offers are allowed to change their structures. Now, imagine if 698 01:06:09,229 --> 01:06:14,859 the protein data bank would be like GitHub with pull requests. We could go like, go 699 01:06:14,859 --> 01:06:18,789 like, changed the molecule around. Go like, no, it's a better fit to your data. 700 01:06:18,789 --> 01:06:22,979 Please pull. Herald: That would be a very subversive 701 01:06:22,979 --> 01:06:26,259 proposition. I would say. Andrea: Yeah, wouldn't that be nice? I'm 702 01:06:26,259 --> 01:06:31,319 like, Why aren't we doing this? It's like the system is already there. It happens 703 01:06:31,319 --> 01:06:35,769 that we have like repositories for a while in software development. We could do the 704 01:06:35,769 --> 01:06:44,049 same thing with models fitted to our experimental data. But I think I need to 705 01:06:44,049 --> 01:06:47,999 go into more committees. melzai_a: Yeah, it sounds like this. I 706 01:06:47,999 --> 01:06:53,839 would agree for that proposal. There was a person that was asking about the toolsset 707 01:06:53,839 --> 01:06:58,539 that you would use to simulate those molecules and structures and so on. And if 708 01:06:58,539 --> 01:07:03,599 you then create these more usable pictures for the public, how do you balance 709 01:07:03,599 --> 01:07:08,449 artist's impression simplified models and while keeping the scientific truth as 710 01:07:08,449 --> 01:07:14,160 much as well as possible. Andrea: The question you don't need the 711 01:07:14,160 --> 01:07:17,719 public even to have this problem. You have it already when you make pictures 712 01:07:17,719 --> 01:07:21,589 scientifically. Because sometimes you want to show our certain aspects of a molecule 713 01:07:21,589 --> 01:07:26,630 very clearly, which means you have to cut away, for example, a part of the molecule. 714 01:07:26,630 --> 01:07:30,979 So one answer to this is the program that does. The modeling is not a program that 715 01:07:30,979 --> 01:07:35,329 you use to make the pictures. That's the first thing you do. So you make your model 716 01:07:35,329 --> 01:07:38,809 with one program and then you take all the coordinates of the atoms and you throw 717 01:07:38,809 --> 01:07:44,569 them into a professional rendering program that like, we'll do it all pretty. But you 718 01:07:44,569 --> 01:07:48,930 still have to make an executive decision on what to show in your graphics, in your 719 01:07:48,930 --> 01:07:56,799 paper. And I think that in particular, structural biologists, who deal with three 720 01:07:56,799 --> 01:08:01,329 dimensional and two-dimensional pictures, we would do very well to think a lot more 721 01:08:01,329 --> 01:08:07,769 about scientific illustration. So all my team likes thinking about these things, 722 01:08:07,769 --> 01:08:12,460 which is, I think, how we got where we are now, right? They actually like stuff like 723 01:08:12,460 --> 01:08:17,890 this. They go like, Oh, we can print it 3D and we can put a magnet on it and it's 724 01:08:17,890 --> 01:08:21,980 going to stick. But it turns out that scientists also need these tools to 725 01:08:21,980 --> 01:08:26,830 understand what's going on. It's like actually having a 3D model helps you so 726 01:08:26,830 --> 01:08:32,420 much with thinking about things. Crick and Watson. They build a model of their DNA in 727 01:08:32,420 --> 01:08:37,160 metal for a reason. Because we're looking at three dimensional things, making them 728 01:08:37,160 --> 01:08:43,560 like understandable with our hands. So yes, as a good researcher, you're not only 729 01:08:43,560 --> 01:08:48,739 able to explain your research to the cleaning woman, you should also be able to 730 01:08:48,739 --> 01:08:53,290 visualize it properly. And it's part of the art. If you are a structural biologist 731 01:08:53,290 --> 01:08:58,310 and you're not able to make good pictures of your molecules, you're not a good 732 01:08:58,310 --> 01:09:02,239 structural biologist. End of story. You're in the wrong discipline, you should have 733 01:09:02,239 --> 01:09:05,359 possibly chosen something where you need less graphics. 734 01:09:05,359 --> 01:09:12,069 melzai_a: And I think one of your industry does is actually a of biologist by 735 01:09:12,069 --> 01:09:17,699 training. Right? I think you've got... Andrea: Tomasello is a proper biologist. 736 01:09:17,699 --> 01:09:25,589 Thomas Splettstössersplit shrews as a prop about like a Ph.D. in bioinformatics and Janet Erosa, 737 01:09:25,589 --> 01:09:32,569 and LiU are both scientists who are having a group that only deals with illustration. 738 01:09:32,569 --> 01:09:36,460 So it's actually in science. We have several groups in the world and structural 739 01:09:36,460 --> 01:09:41,690 biology who only do illustration as science. So David Goodsell with his 740 01:09:41,690 --> 01:09:48,179 watercolors, is very well known, but Janet Erosa is another one. So actually making 741 01:09:48,179 --> 01:09:54,880 these animations and pictures is so complicated that television can't do it. 742 01:09:54,880 --> 01:10:00,480 And the ZDF made a series of animations, so they made very nice ones for Planet E 743 01:10:00,480 --> 01:10:06,090 Rizzo and Nano with us. But then they asked my expertize to make another 744 01:10:06,090 --> 01:10:11,429 animation. And they only had like a call with us, and they never came back and then 745 01:10:11,429 --> 01:10:18,630 published a completely wrong animation of the entire viral mechanism under my name. 746 01:10:18,630 --> 01:10:24,690 And I'm still sad every time I see it three times a day. Heute Journal shows a 747 01:10:24,690 --> 01:10:29,469 wrong structure of the virus for which they claim that I helped them make it, and 748 01:10:29,469 --> 01:10:34,530 I wrote to them and told them, Your depiction of the virus is wrong. I can 749 01:10:34,530 --> 01:10:43,199 help you make a new one. But it seems that it's 2. deutsche Fernsehen der heute Journal at least didn't 750 01:10:43,199 --> 01:10:49,830 care on. I guess they think it's not important enough, but I think with a 751 01:10:49,830 --> 01:10:55,050 threat like this where we really cannot see the virus, it is important to bring to 752 01:10:55,050 --> 01:11:00,679 the public the best possible depiction we can deliver. Sometimes, however, as I 753 01:11:00,679 --> 01:11:05,010 said, you omit certain aspects, for example, to show the effects of a mutation 754 01:11:05,010 --> 01:11:12,619 yet only showed a side of the mutation. You don't show all the atoms. But. That's 755 01:11:12,619 --> 01:11:15,830 really an important part of what we are doing. Like pointing out the important 756 01:11:15,830 --> 01:11:18,130 bits of ... melzai_a: Scientific information is so 757 01:11:18,130 --> 01:11:23,900 important, I think we have one final question, which I would say comes out 758 01:11:23,900 --> 01:11:30,460 comes towards the direction of the immune system. And the question would be can you 759 01:11:30,460 --> 01:11:35,949 can you define vaccine on purpose so that the immune system can forget how to 760 01:11:35,949 --> 01:11:39,889 produce the antibodies after a defined period of time? And I think the concern 761 01:11:39,889 --> 01:11:48,670 here is about increasing your financial gain in the crisis, for example. 762 01:11:48,670 --> 01:11:55,540 So programed obsolescence, as both of those mentioned. So you're a bit late. So 763 01:11:55,540 --> 01:12:00,800 if you could keep it short, that would be great. OK? Andrea: The quick answer is no, 764 01:12:00,800 --> 01:12:08,480 that's not possible. You can make. You can enhance how long vaccines and how much 765 01:12:08,480 --> 01:12:13,929 immune response you get from a vaccine or certain additives. But you can not, like 766 01:12:13,929 --> 01:12:18,810 make them a definite time because everybody is different. So even when you 767 01:12:18,810 --> 01:12:21,840 get your booster shot, they say six months, but you may need it after three 768 01:12:21,840 --> 01:12:27,550 months or you may need it after 12 authorityto. It's very hard to tell. And 769 01:12:27,550 --> 01:12:32,520 pharma industry does not have tools that would allow them that, to my knowledge. So 770 01:12:32,520 --> 01:12:38,690 I think that's not a risk. melzai_a: I mean, it's it's a human 771 01:12:38,690 --> 01:12:43,780 system, and so complex is the rocket to the Moon. So. 772 01:12:43,780 --> 01:12:46,860 Andrea: I think it's a it's a valid concern. It's just technologically not 773 01:12:46,860 --> 01:12:53,429 possible. Luckily, I guess. melzai_a: The final and really last question, I think, 774 01:12:53,429 --> 01:12:57,110 is where can somebody find the 3D models out there? 775 01:12:57,110 --> 01:13:01,780 Andrea: Oh, you can go to inside Corona..de and find a blog post about a 3D 776 01:13:01,780 --> 01:13:13,050 thing or you go to Thingy Reuss and you look for inside corona. I can. Yeah. Yeah. 777 01:13:13,050 --> 01:13:21,110 I just go to. I just put it in. Why not that? That's our home page and then on 778 01:13:21,110 --> 01:13:29,380 thingy worse. It's also called inside corona. And you can also write me a 779 01:13:29,380 --> 01:13:36,860 message on Twitter if you don't find it at a turn up. And remember, we're going to 780 01:13:36,860 --> 01:13:43,260 put out a new model soon in January, but I'm still waiting for the final files and 781 01:13:43,260 --> 01:13:49,840 holiday. So it will be a few more weeks. melzai_a: So but that trend in January, 782 01:13:49,840 --> 01:13:53,260 not in December 2008. Yeah, exactly. Or printed? 783 01:13:53,260 --> 01:13:59,960 Andrea: Yes. So thank you very much for having me. 784 01:13:59,960 --> 01:14:02,820 melzai_a: Yeah, it was good. Thank you. And I think if they are no more questions. 785 01:14:02,820 --> 01:14:08,280 Everybody. All right. Oh, you know how it looks like? I think that's really 786 01:14:08,280 --> 01:14:12,020 important. I think one and a half years ago, I came across the first pictures was 787 01:14:12,020 --> 01:14:17,710 like, This is how it looks like. Now I can tell it to the people who who don't read 788 01:14:17,710 --> 01:14:26,090 the scientific original papers because they are so difficult to read. So. Yeah. 789 01:14:26,090 --> 01:14:34,130 Good. You know. And thanks for being here and looking forward to hearing and seeing 790 01:14:34,130 --> 01:14:38,050 more and hopefully once this will be over. I think 791 01:14:38,050 --> 01:14:43,730 Andrea: I hope so too. Going back out of the spotlight to being just a Methods 792 01:14:43,730 --> 01:14:45,730 developer, that would be nice. Herald: That would be nice, yes. 793 01:14:45,730 --> 01:15:05,000 Subtitles created by c3subtitles.de in the year 2022. Join, and help us!