0:00:24.900,0:00:30.060
Herald: So, willkommen zusammen. Heute[br]Abend gibt es den Talk von Andrea über den

0:00:30.060,0:00:35.489
"Corona Virus Structural Task Force". Ich[br]bin melzai_a Herald für die Session. Wir

0:00:35.489,0:00:40.030
haben einen Signal Angel, Dia, sie wird[br]die Fragen sammeln, die in den Chat

0:00:40.030,0:00:45.010
gestellt werden und am Ende gehen wir im[br]Vortrag über diese Fragen. So viel zum

0:00:45.010,0:00:51.530
Ablauf. Der Vortrag wird aufgezeichnet.[br]Und ist danach nachträglich verfügbar auf

0:00:51.530,0:00:58.223
Media.ccc.de irgendwann in den nächsten[br]Tagen oder Wochen. Und damit würde ich mich

0:00:58.223,0:01:01.730
freuen, Andrea, du als[br]Nachwuchsruppenleiterin an der Uni

0:01:01.730,0:01:04.670
Hamburg, du hast die letzten zwei Jahre[br]mit den Codona Virus beschäftigt, und

0:01:04.670,0:01:09.970
daraus wunderbare Visualisierung gemacht.[br]Wie lief es denn ab und wie sieht Corona

0:01:09.970,0:01:12.220
eigentlich aus?

0:01:12.220,0:01:17.049
Andrea: Ja, vielen dank! Erstmal danke für[br]die Einladung. Und ja, genau darum geht es

0:01:17.049,0:01:27.170
in dem Talk jetzt, was wir die "corona[br]virus structure task force" nennen. I'm

0:01:27.170,0:01:30.990
going to give the presentation in English;[br]so that international listeners can also

0:01:30.990,0:01:37.460
listen in. But you can ask your questions[br]in, well, any language anyone here speaks.

0:01:37.460,0:01:44.690
I understand German, English and Japanese.[br]And I want to start with a quote by Marie

0:01:44.690,0:01:52.620
Curie. I know the room Mary is not named[br]after Marie Curie, but she said something

0:01:52.620,0:01:57.850
that is very true in this pandemic, which[br]is: "nothing in life, is to be feared,

0:01:57.850,0:02:06.570
only to be understood. Now is the time to[br]understand more so that we may fear less."

0:02:06.570,0:02:12.110
And indeed, this holds true for the corona[br]virus more than anything, because as you

0:02:12.110,0:02:18.190
all know, you cannot see the virus. You[br]can only see it indirectly visualized by

0:02:18.190,0:02:25.490
science or you can see the measures against[br]it or you can see ill people. But the

0:02:25.490,0:02:31.550
virus itself is invisible. And I'm going[br]to start this talk with questions. There

0:02:31.550,0:02:39.290
will be many questions. And the first one[br]is, what does the corona virus look like?

0:02:39.290,0:02:44.989
Now you may think, you know, but the[br]reality of it is that even German news has

0:02:44.989,0:02:50.499
no idea. And I know that ZDF is now using[br]a different picture, which looks more

0:02:50.499,0:02:58.099
similar to what I'm going to show, but[br]it's very wrong as well. This picture? Is

0:02:58.099,0:03:02.379
what most people think the virus looks[br]like. And I also brought you like two top

0:03:02.379,0:03:09.799
model and models of the virus. One can[br]even make sounds. Any spiky ball of

0:03:09.799,0:03:15.519
this days really passes as a corona virus[br]because no one seems to know what the

0:03:15.519,0:03:22.519
thing really looks like. Only it's like[br]crowned. And it has spikes. That's the

0:03:22.519,0:03:26.700
only thing that all the models have in[br]common. But some things look like you can

0:03:26.700,0:03:32.520
just, you know, like they are little Shrek[br]ears type things or have tentacles. No

0:03:32.520,0:03:39.539
one really knows. So how do we know as[br]scientists and can viruses, be seen? If we

0:03:39.539,0:03:45.249
imagine so, this is an electron[br]microscopic picture of a human hair. It's

0:03:45.249,0:03:53.419
0.1 millimeters. It's the length of this[br]line, so the hair is a little bit less.

0:03:53.419,0:03:58.040
The little red dot, which you may or may[br]not be able to see inside that circle is

0:03:58.040,0:04:02.670
the size of the corona virus. Now if we[br]zoom into the picture of the hair, you can

0:04:02.670,0:04:10.279
see, I hope, a little red dot here. And[br]that's the corona virus to measure. So it

0:04:10.279,0:04:18.739
is 150 nanometers, or 0.0001.5 mm large. That is tiny

0:04:18.739,0:04:26.950
even by scientists sentence. However. Even[br]smaller than the virus with 150

0:04:26.950,0:04:32.440
nanometers. It's a single atom,[br]which is represented here again by a

0:04:32.440,0:04:40.889
dot, which is barely visible and is 0.1[br]nanometers in diameter or one. Angstrom.

0:04:40.889,0:04:46.620
Atoms are tiny, even compared to the[br]virus. A virus is composed being matter of

0:04:46.620,0:04:53.010
very, very many atoms. How can we[br]visualize something this small? Can we see

0:04:53.010,0:04:59.840
it with a light microscope? And what color[br]would the virus be? This is to scale.

0:04:59.840,0:05:04.580
Yellow light. It is 600 nanometer[br]wavelength meaning from this point to

0:05:04.580,0:05:09.650
this, it is 600 nanometers. So the[br]wavelength of visible light, which ranges

0:05:09.650,0:05:19.080
from 400 to 780 nano meters, is actually[br]longer than the virus is white. So there

0:05:19.080,0:05:27.090
is no chance whatsoever to ever observe a[br]single virus with light just physically

0:05:27.090,0:05:33.449
not possible. We need something that has a[br]smaller wavelength, and there are two

0:05:33.449,0:05:40.819
things we use X-rays, which have 0.1 nanometer wavelength. So they

0:05:40.819,0:05:45.870
are very, very small. They're like light. They're also photons. We call it

0:05:45.870,0:05:53.190
also X-ray light (Röntgenstralung,[br]Röntgenlicht). But they have so high energy

0:05:53.190,0:05:58.270
that their wavelengths are tiny. The other[br]thing are electrons, which have even

0:05:58.270,0:06:02.680
smaller wavelengths. If you choose to[br]regard them not as particles, but as

0:06:02.680,0:06:07.739
waves. So we can use electrons and X-rays[br]to observe the virus, and we do. And for

0:06:07.739,0:06:12.710
this, we have several possibilities. One[br]of them is large particle accelerators

0:06:12.710,0:06:17.199
like the one I'm working on in Hamburg,[br]which produces very intense X-rays.

0:06:17.199,0:06:23.080
Another one is an electron microscope. So[br]here is a model of an electron microscope.

0:06:23.080,0:06:29.730
In order to use it, you need a scientist[br]and then you shoot an electron beam from

0:06:29.730,0:06:34.750
an electron cannon. That's the official[br]scientific term. It's an electron cannon

0:06:34.750,0:06:40.909
onto both an electron gun electron cannon[br]electron gun. You shoot your electrons

0:06:40.909,0:06:44.760
through lenses, which are magnetic.[br]Electrons are negatively charged so the

0:06:44.760,0:06:50.710
magnetic field can be used as a lens[br]system onto a sample. For example, the

0:06:50.710,0:06:57.120
virus and then you have a detector. What[br]do we see on this detector? We should

0:06:57.120,0:07:03.580
viruses with electrons and record how many[br]electrons pass through the sample? What we

0:07:03.580,0:07:07.520
see looks like this. So of course, it's[br]black and white because electrons come.

0:07:07.520,0:07:14.740
There's no colors involved. And what you[br]can see is a dark shadow. And then around

0:07:14.740,0:07:22.780
it, a little bit of bright spots, almost[br]like a corona during a sun eclipse. So

0:07:22.780,0:07:27.879
this is why the corona virus is called[br]corona virus, because it spikes under the

0:07:27.879,0:07:34.219
electron microscope look like a corona.[br]And these pictures have no colors, but

0:07:34.219,0:07:37.740
scientists like to colored them in[br]particular in order to tell people that

0:07:37.740,0:07:42.319
this is a dangerous virus and that is the[br]background. So if we colored, it may look

0:07:42.319,0:07:48.810
like this. And this is an official picture[br]released very early in the pandemic by the

0:07:48.810,0:07:57.360
National Institutes as one of the first[br]pictures of the new corona virus. We can

0:07:57.360,0:08:01.360
also do scanning electron microscopy,[br]which is a similar measure where you coat

0:08:01.360,0:08:06.840
the entire surface and then you get a[br]pretty three dimensional picture. What you

0:08:06.840,0:08:11.189
can see here are lung cells, the lung[br]carpet like the like hairy structure here.

0:08:11.189,0:08:17.960
That's lung cells that are single type two[br]alveolar epithelial cells. So there are

0:08:17.960,0:08:23.110
like a little like their job is to[br]get rid of stuff the lungs don't want

0:08:23.110,0:08:28.710
there, like a carpet, they can move and[br]they get rid of stuff for you. However,

0:08:28.710,0:08:32.830
these cells, you have a problem. They're[br]infected with corona virus. You can see

0:08:32.830,0:08:41.040
some slime or mucus here, and you can see[br]the viruses here. Because of the coating,

0:08:41.040,0:08:45.680
they look a little bit like cauliflower.[br]So that's nice. But it doesn't give us the

0:08:45.680,0:08:50.310
full picture, but so much for people who[br]say we cannot isolate the virus. We can

0:08:50.310,0:08:57.860
actually even like, make it visible. So we[br]can make this invisible enemy visible. It

0:08:57.860,0:09:02.390
is just a question of having the right[br]equipment and a good sample of the virus

0:09:02.390,0:09:07.830
and many hours of work. The virus[br]therefore exists and can be made visible

0:09:07.830,0:09:12.400
using electron microscopes or, for[br]example, as a particle accelerator. But

0:09:12.400,0:09:16.530
I'm not going to go into detail here. We[br]have not enough time tonight. I'm only

0:09:16.530,0:09:25.250
going to talk about electron microscopes[br]here. So what is the virus made of. Those

0:09:25.250,0:09:30.260
This is the virus. We're going to talk about[br]this picture later in the talk when we

0:09:30.260,0:09:35.080
talk about model a little bit more. But[br]here is one Spike, I think you've all

0:09:35.080,0:09:41.530
heard in news from spike proteins, which[br]cover the surface of the virus or the

0:09:41.530,0:09:48.820
virion. If we draw this schematically, as[br]Thomas Splettstösser presented for us, he's an

0:09:48.820,0:09:54.080
illustrator, burst in Berlin, it looks[br]like this. And then we take only the head

0:09:54.080,0:09:58.750
of the spike, which is the region of the[br]spike we know most about, and then comes

0:09:58.750,0:10:03.130
an animation that I did. So it's not quite[br]as pretty. If we zoom in, we see the

0:10:03.130,0:10:09.730
surface and below that surface we see[br]things represented as a ribbon. However,

0:10:09.730,0:10:13.810
we can show this differently. We can show[br]the individual atoms connected to each

0:10:13.810,0:10:19.730
other. The problem with this display is[br]that it's really hard to find anything

0:10:19.730,0:10:25.560
here. It is super difficult to get an[br]overview with this picture, so we prefer

0:10:25.560,0:10:32.470
to show these complicated and fake[br]molecules made up of atoms as surfaces and

0:10:32.470,0:10:38.570
ribbons. And this ribbon diagram, by the[br]way, has also been found by a great female

0:10:38.570,0:10:42.980
scientist, Jane Richardson, several[br]decades ago, which was quite revolutionary

0:10:42.980,0:10:48.519
for my field. So the virus is made up of[br]atoms and molecules, and they are

0:10:48.519,0:10:55.060
structures can be found out by NMR, X-ray[br]crystallography and electron microscopy.

0:10:55.060,0:11:00.120
For now, this is all I'm going to tell[br]you. We're now going to dive very deeply

0:11:00.120,0:11:05.330
into the biology of the virus and what the[br]structures tell us. And then in the end,

0:11:05.330,0:11:09.830
I'm going to tell you a little bit more[br]exactly how we actually get from the

0:11:09.830,0:11:17.880
measurement to the model, which holds some[br]pitfalls and problems for us. And it's an

0:11:17.880,0:11:23.320
area in which I do usually my research.[br]But first, I'm going to talk about the

0:11:23.320,0:11:29.220
model, you all know this picture from the[br]CDC, right? And by the way, this thing for

0:11:29.220,0:11:33.640
a scientist, this thing is not a virus,[br]it's a variant. It's only the transport

0:11:33.640,0:11:38.630
form of the virus, the virus. That's a few[br]more things that are not contained in this

0:11:38.630,0:11:44.630
little show. That's just a transport form[br]for its RNA to get into a whole cell. We

0:11:44.630,0:11:48.050
call this a variant. But most people, even[br]scientists, can also refer to it as the

0:11:48.050,0:11:55.690
virus. So this is the CDC model, right?[br]That's the picture that went all through

0:11:55.690,0:12:00.940
the press around the world. That's like[br]THE picture of this pandemic, and it was

0:12:00.940,0:12:06.970
made by the CDC very early on by two[br]scientific illustrators there. However,

0:12:06.970,0:12:11.950
already then it had some problems. They[br]made it in quite a rash and it has some

0:12:11.950,0:12:22.470
errors. So we decided to make a new[br]picture, which looks like this. And. If

0:12:22.470,0:12:28.560
you compare it, two pictures, here are the[br]differences. The head of the spike in this

0:12:28.560,0:12:33.700
illustration sits directly into the[br]surface, while in reality it is singing

0:12:33.700,0:12:42.050
sitting on a long, very bendy like rope[br]like structure that tethers it. So the

0:12:42.050,0:12:46.750
virus, the head of the spike, which binds[br]to the host cell, is quite flexible. The

0:12:46.750,0:12:51.470
surface is not quite as coarse as shown[br]here. It's smaller. The virus actually

0:12:51.470,0:12:58.140
relatively large for a virus, and it's got[br]other proteins swimming in its surface. If

0:12:58.140,0:13:04.320
you look exactly, you'll see the virus is[br]also not exactly round. Now we thought

0:13:04.320,0:13:07.550
this is not enough. It's nice to have a[br]picture, but wouldn't it be nice if we

0:13:07.550,0:13:12.830
could actually touch it? So we made a 3D[br]printable model for those interested. You

0:13:12.830,0:13:18.780
can find also all that information on our[br]homepage. I'm going to show you the 3D

0:13:18.780,0:13:26.880
model. Let's see. So. This is the virus[br]model. As you can see, the virus is not

0:13:26.880,0:13:33.360
exactly round because it's outside, it's[br]very soft. It's like a soap bubble. It can

0:13:33.360,0:13:39.140
change its shape quite drastically. It's[br]wobbly and the spikes are actually

0:13:39.140,0:13:42.860
stochastic highly distributed. They're not[br]like regularly arranged and they are

0:13:42.860,0:13:49.500
swimming in the skin. And there are other[br]proteins in the surface as well, which you

0:13:49.500,0:13:55.670
can perhaps see whether they really formed[br]as little flower shapes, we don't know.

0:13:55.670,0:14:01.980
And the virus is huge. So this on the same[br]scale, one to one million as a rhinovirus

0:14:01.980,0:14:08.510
for the common cold. The corona virus is[br]huge. 20000 base pairs RNA makes it one of

0:14:08.510,0:14:15.420
the largest virus genomes we know. And a[br]virus, therefore as soft on the outside,

0:14:15.420,0:14:23.720
while rhinovirus has a very hard and rigid[br]shell that is always composed the same.

0:14:23.720,0:14:28.440
And we need this model in the hopes that,[br]like other scientists and perhaps schools

0:14:28.440,0:14:34.250
would like to print it at home and[br]actually like, get something tangible and

0:14:34.250,0:14:39.170
it turned out they did. So we got quite a[br]few requests from people, from child care

0:14:39.170,0:14:43.830
facilities and from schools and from other[br]scientists. And even my administration

0:14:43.830,0:14:47.850
like to have them printed. One even[br]proposed we may have them as Christmas

0:14:47.850,0:14:55.560
ornaments, but I found that a little bit[br]like tasteless. We didn't do it. And like,

0:14:55.560,0:15:01.230
just before I left Hamburg, we got a new[br]model. This model is now already a year

0:15:01.230,0:15:07.050
old, and in 2021, signs made quite a lot[br]of progress. So we now know there are

0:15:07.050,0:15:11.110
fewer spikes and a virus. All in all, it's[br]a little bit smaller, so it's not quite

0:15:11.110,0:15:16.020
like this, but perhaps less so. It's not[br]15 centimeters in diameter. The model is

0:15:16.020,0:15:21.300
12, and it is still like potato shaped.[br]It's not round because now what's

0:15:21.300,0:15:26.640
important for me to show, and I would have[br]like to show you this model like in front

0:15:26.640,0:15:33.160
of the camera tonight, but. It went into[br]the museum, it was the first one we had,

0:15:33.160,0:15:37.420
and we brought it to the opening of this[br]exhibition in Hamburg "Pandemierück in ide

0:15:37.420,0:15:41.370
Gegenwart" the gigawatt, so you can now[br]see it in the museum and we'll be back in

0:15:41.370,0:15:48.840
my office when they have assembled theres.[br]And this also holds true. I'm going to

0:15:48.840,0:15:52.560
talk about the task force in the second[br]half of this talk. But one thing that is

0:15:52.560,0:15:56.930
really true and what's true for this[br]project as well is the task force is

0:15:56.930,0:16:01.220
typically more interested in new[br]communication projects than in all the

0:16:01.220,0:16:07.500
pile of stuff we need to finish. You may[br]notice from home. Right. So this is how

0:16:07.500,0:16:14.280
our model. Now, let's dive deeper into the[br]thing, because so far we have only talked

0:16:14.280,0:16:20.630
about the virion and only about it's[br]outside. So the virion has to spike

0:16:20.630,0:16:27.200
proteins on the outside. Two other[br]proteins M and E protein, it has a double

0:16:27.200,0:16:34.230
membrane hull, which is very thin and[br]nucleocapsid, which is wrapping the RNA.

0:16:34.230,0:16:38.800
The RNA of actually containing the genes[br]for everything that the virus needs in

0:16:38.800,0:16:45.950
order to like, take possession of the host[br]cell. So the RNA is the important bit the

0:16:45.950,0:16:51.250
virion is transporting and nucleocapsid[br]and everything else kind of packs it and

0:16:51.250,0:16:58.710
makes sure it gets into the host cell. And[br]I'm going to show you quickly a video

0:16:58.710,0:17:03.850
because I think this is so nice to[br]understand, and it's the answer to the

0:17:03.850,0:17:09.600
question why does soap help against corona[br]virus? Because very many, like other

0:17:09.600,0:17:15.419
viruses, are relatively hard to wash off,[br]but not corona virus, because it's so

0:17:15.419,0:17:20.280
large, it has only a double membrane[br]shell. And this is a very nice video from

0:17:20.280,0:17:25.280
the protein data bank from our colleagues[br]there. So this is the virus double

0:17:25.280,0:17:31.430
membrane. It has lipid molecules. You can[br]see there are hydrophobic on the inside

0:17:31.430,0:17:36.270
and hydrophilic on the outside, so they[br]lock water on the outside, but not the

0:17:36.270,0:17:42.600
inside. Green molecules are soap. Soap[br]also has a hydrophobic tail and a

0:17:42.600,0:17:48.280
hydrophilic head. So unlike the water[br]which stays outside the soap just gets

0:17:48.280,0:17:54.280
into the membrane and kind of like goes in[br]between the lipids. And then they make

0:17:54.280,0:18:01.040
whole sort of water molecules can get[br]inside the virus. They can even assemble.

0:18:01.040,0:18:09.550
In around bits of the membrane and get it[br]out of the virus hull or around a spike

0:18:09.550,0:18:16.280
and remove to spike, which is hydrophobic[br]to stock out of the virus. This leads to a

0:18:16.280,0:18:21.340
total decomposition of the membrane and[br]therefore it can be completely dissolved

0:18:21.340,0:18:27.640
by soap. As soon as the nucleocapsid and[br]an RNA are exposed, the virus is no longer

0:18:27.640,0:18:34.610
infectious. It needs a spike in order to[br]infect so, you don't need to disinfect

0:18:34.610,0:18:39.980
your hands. You can just wash them with[br]soap, which I find is so lucky in this

0:18:39.980,0:18:44.410
pandemic because, you know, it would be[br]really ugly if we would need to disinfect

0:18:44.410,0:18:50.230
everything all the time, but we can[br]actually just use soapy water. Although,

0:18:50.230,0:18:55.750
let's be honest, I like to use[br]disinfectant every here, and then it gives

0:18:55.750,0:19:01.250
me just a feeling of more safety. It's[br]kind of like a ritual to protect me. I

0:19:01.250,0:19:09.910
suspect several of you are the same. So,[br]so much for the virion, that's like the

0:19:09.910,0:19:17.560
outer shell, that's like the transport[br]form. But there is more much more. This is

0:19:17.560,0:19:21.140
the corona virus life cycle, or I should[br]be more correct. It should be called

0:19:21.140,0:19:25.900
infection cycle because technically[br]speaking, viruses are not life. They need

0:19:25.900,0:19:31.520
a host cell to reproduce. So we're going[br]to come back to this picture. We're going

0:19:31.520,0:19:40.270
to take this apart bit by bit. First of[br]all, there is entry entry into oh yeah.

0:19:40.270,0:19:44.560
Let's quickly go back. The thing at the[br]bottom here, the big thing here. That's

0:19:44.560,0:19:48.510
the host cell. And a little one is[br]the virus, right? We're clear on that

0:19:48.510,0:19:51.610
Holbrook's here, right? And is the[br]outside. So this is like your lung

0:19:51.610,0:19:56.640
outside. That's your lung cell inside or[br]hopefully not your lung cell, right?

0:19:56.640,0:20:04.340
There's the virus. And this is the spike,[br]the spike as a vaccine target, as you

0:20:04.340,0:20:10.270
know, it's what's encoded in RNA vaccines[br]and it's also contained in all the like

0:20:10.270,0:20:17.440
vector vaccines we see. And I brought you[br]another model for that, which saw the

0:20:17.440,0:20:28.680
picture here. So this is one to 10 million[br]scale model of the spike. And this is an

0:20:28.680,0:20:36.440
antibody. Now if you are vaccinated either[br]by RNA or by a vector vaccine, your body

0:20:36.440,0:20:42.110
overproduce as far as injected with[br]spikes, which are usually on something to

0:20:42.110,0:20:48.950
carry it a host cell or a cell of your[br]body if it's an RNA vaccine or a vector.

0:20:48.950,0:20:54.290
Your body needs a few days to recognize[br]this thing, so once it has, it will build

0:20:54.290,0:21:00.290
antibodies that perfectly fit onto that[br]they can recognize the spike very, very

0:21:00.290,0:21:04.190
exactly. They have a specific binding[br]site, which is much more rigid than

0:21:04.190,0:21:11.090
anything else the antibody can bind to.[br]Then this gets decomposed because the

0:21:11.090,0:21:16.260
vaccine is not viable. What remains in[br]your body is information for these

0:21:16.260,0:21:24.200
antibodies. So now if you get infected[br]with corona? The immune system antibody

0:21:24.200,0:21:28.710
recognizes the spike it has previously[br]seen in the vaccine, and that is how the

0:21:28.710,0:21:35.930
vaccine actually works. So having this[br]protects you, one of the biggest problems

0:21:35.930,0:21:41.140
with COVID 19 infections is that the[br]immune system responds too late. And then

0:21:41.140,0:21:47.730
too much. So having these makes much more[br]certain that you will not get severe

0:21:47.730,0:21:55.960
COVID, which is, I think, very nice. And[br]what we also did, together with the

0:21:55.960,0:22:01.720
animation lab in Utah is not only make[br]those life life cycle or infection cycle,

0:22:01.720,0:22:06.130
we also made an animation the[br]scientifically most accurate animation

0:22:06.130,0:22:11.850
available on how the virus actually binds[br]onto the whole cell. There's a lot we

0:22:11.850,0:22:18.450
don't know, but everything we do know we[br]have shown here. So here is the virus. You

0:22:18.450,0:22:26.320
know the spike protein already. Yes,[br]nucleocapsid inside there is RNA, which

0:22:26.320,0:22:32.220
encodes for the rest, we're going to go[br]into the rest after this. And then at the

0:22:32.220,0:22:37.820
bottom here is the host cell. So lung[br]cells actually have ACE2 receptors shown

0:22:37.820,0:22:43.750
in purple, and a spike protein recognizes[br]those specifically meaning that items like

0:22:43.750,0:22:53.840
a puzzle piece fit exactly onto the purple[br]receptors on the lung cells. The spikes

0:22:53.840,0:23:01.710
bind there and then something else[br]happens. Another enzyme also being in the

0:23:01.710,0:23:07.220
membrane of the host cell cuts the spike,[br]so it's not like the name spike suggests

0:23:07.220,0:23:12.320
it would like shoot something into. But[br]that's not the case. It gets cut and then

0:23:12.320,0:23:16.250
comes to bed where we are a little bit[br]unclear how this happens. So what we know

0:23:16.250,0:23:20.300
is after it's cut, it somehow ends up[br]being tethered into the host cell and we

0:23:20.300,0:23:24.870
don't know the mechanism of this. So we[br]decided to illustrated here with like a

0:23:24.870,0:23:31.480
refolding process and then it's[br]energetically unstable. So in order to

0:23:31.480,0:23:36.470
become more stable, the whole thing clamps[br]and folds together, thereby dragging the

0:23:36.470,0:23:41.820
virus and the host cell membrane together,[br]the two membranes to buy a lipid membranes

0:23:41.820,0:23:49.560
Fuze. The virus material is inserted into[br]the cell. The RNA is now inside the host

0:23:49.560,0:23:57.050
cell, and this is how infection happens.[br]So we felt it was particularly important

0:23:57.050,0:24:01.930
to show this to people. We have made this[br]animation Creative Commons, but

0:24:01.930,0:24:06.160
unfortunately only American television[br]caught up on it, so we're really hoping

0:24:06.160,0:24:10.250
that one of the German like documentaries[br]will show this, because we think it's

0:24:10.250,0:24:19.870
really nice to see this process like as[br]accurately as we can depicted. So here is

0:24:19.870,0:24:24.809
the spike. That's the role of the spike.[br]Now the nucleocapsid, an RNA a half

0:24:24.809,0:24:32.760
entered into the host cell. What happens[br]now is that the nucleocapsid dissolves.

0:24:32.760,0:24:38.170
How that exactly happens, we don't know,[br]but it dissolves and RNA gets immediately

0:24:38.170,0:24:45.030
translated into protein. So the genome[br]gets RET inside the cell because the cell

0:24:45.030,0:24:49.700
believes it's own either comes from the[br]host cell and it starts building. The

0:24:49.700,0:24:54.100
proteins encoded in proteins are again[br]molecules. And actually, it makes one

0:24:54.100,0:25:00.600
very, very long protein chain really long,[br]which is called the poly protein, which

0:25:00.600,0:25:06.590
then gets cleaved. So D'Souza's in this[br]case, the thing that cleaves all the long

0:25:06.590,0:25:11.610
protein chain into individual molecules[br]that don't actually can work is called the

0:25:11.610,0:25:16.970
main protease because it's cutting protein[br]that's called the protease. And these are

0:25:16.970,0:25:22.150
the little triangle shaped things here.[br]Only when that happens to these bits

0:25:22.150,0:25:26.890
become functional. So if it doesn't[br]happen, if we can like hindered this like

0:25:26.890,0:25:33.010
cutting off the long polypeptide chain, we[br]have an efficient drug against corona,

0:25:33.010,0:25:37.880
which is why main protease is a major drug[br]target. And what you can see here in red

0:25:37.880,0:25:44.510
is the drug actually bound two main[br]protease. So that's what it looks like. We

0:25:44.510,0:25:48.220
are looking specifically for inhibitors,[br]which will stop this molecule from

0:25:48.220,0:25:52.150
function. So you can imagine this like a[br]screwdriver that we put out of right point

0:25:52.150,0:25:57.910
in a machine where it fits and it stops[br]the entire machinery. That's what we want.

0:25:57.910,0:26:01.610
And that's like called structure based[br]drug design. When you actually know the

0:26:01.610,0:26:06.220
structure of the molecule and then you[br]find a molecule, a small molecule, a drug

0:26:06.220,0:26:13.221
molecule that specifically stops whatever[br]that protein molecule is doing. It's also

0:26:13.221,0:26:21.230
how many antibiotics work or, for example,[br]if you've been up long yesterday aspirin.

0:26:21.230,0:26:29.310
Then. From here, where we have the poly[br]protein thing. Something happens inside

0:26:29.310,0:26:33.830
the cell, the cell is making some kind of[br]foam, which is connected to the

0:26:33.830,0:26:39.940
endoplasmic reticulum. That's just warm[br]and inside it. These like enzymes that

0:26:39.940,0:26:44.330
have now been cut in our functional start,[br]like a copy machine to make more and more

0:26:44.330,0:26:49.820
copies of the RNA genome of the virus. The[br]whole cell kind of like foams up and makes

0:26:49.820,0:26:56.640
more RNA. And it does so by a copy[br]machine, which is called RNA polymerase,

0:26:56.640,0:27:04.950
because RNA is a polymer and a polymerase[br]is an enzyme that's making polymers and an

0:27:04.950,0:27:13.850
RNA polymerase is an enzyme that makes[br]more RNA. So one way to block that process

0:27:13.850,0:27:18.990
of making more RNAs, which was similarly,[br]you know, stop the infection cycle because

0:27:18.990,0:27:24.170
if it can't produce more RNA, it's got[br]nothing to put into new viruses is to use

0:27:24.170,0:27:29.230
remdesivir or so we thought for a long[br]time. So does this remdesivir. Remdesivir

0:27:29.230,0:27:35.950
looks to the host cell and to RNA[br]polymerase in particular, like a

0:27:35.950,0:27:41.710
nucleotide, like a building block for RNA.[br]So basically, things are it's new paper it

0:27:41.710,0:27:47.290
can copy on when in reality it's kind of[br]explosive like blocks the entire

0:27:47.290,0:27:52.770
polymerase. So you can imagine this like a[br]Trojan horse, remdesivir is the Trojan

0:27:52.770,0:27:58.809
horse and RNA dependent RNA polymerase is[br]sure looks like RNA to me and just built

0:27:58.809,0:28:05.500
that into the strand. So we'll have a look[br]at this molecule. This is, by the way, I

0:28:05.500,0:28:10.240
should probably go back and explain this[br]for a moment. This is what we get out of

0:28:10.240,0:28:15.230
our measurements and electron microscopy.[br]So this is the so-called reconstruction

0:28:15.230,0:28:18.790
density, and that's what we built a[br]molecule in. So that's like what the

0:28:18.790,0:28:23.450
measurement gave us, everything else we[br]have to do by hand. So here is the

0:28:23.450,0:28:31.070
density, and this is what the researcher[br]built into it. The template strand, the

0:28:31.070,0:28:36.870
old one, which is to be copied, is green,[br]the new one is orange. Remdesivir is

0:28:36.870,0:28:43.080
purple and connected to the end, although[br]the program doesn't display it as such.

0:28:43.080,0:28:46.880
What you can also see is free magnesium[br]ions. That's their own thing and a de

0:28:46.880,0:28:54.110
phosphate. So what are more molecules that[br]researchers modeled in there? Where are

0:28:54.110,0:28:58.130
around it as the protein? So I've just[br]quickly depicted it without so you can see

0:28:58.130,0:29:01.940
what's happening because it's all very[br]crowded and difficult to see around it as

0:29:01.940,0:29:07.330
the protein and a jump of two proteins to[br]copy the RNA and to attach one after the

0:29:07.330,0:29:11.960
other, another building block to the[br]bottom of the orange chain. It's gotten a

0:29:11.960,0:29:17.149
remdesivir and it tried to put it there[br]and it successfully did. And this

0:29:17.149,0:29:22.220
structure was taken as to prove that[br]remdesivir will stop corona. But if you

0:29:22.220,0:29:26.110
look at the density, you can see that the[br]free magnesium ions and DIPHOSPHATE has no

0:29:26.110,0:29:32.220
density and are not covered by this great[br]cloud, right? So we think they were never

0:29:32.220,0:29:39.140
really there. And the remdesivir itself is[br]also not having so much density. So it

0:29:39.140,0:29:43.120
turns out that a structure is not quite[br]seeing what the researchers did because

0:29:43.120,0:29:48.330
the density doesn't match up with the[br]structure they built. And as we later

0:29:48.330,0:29:53.090
found out in clinical trials, is that[br]remdesivir, in fact, doesn't really do

0:29:53.090,0:29:58.280
what people hoped, which, among other[br]things, has to do with the fact that RNA

0:29:58.280,0:30:03.100
polymerase from corona virus is able to[br]proofread go like, Oh, there's a

0:30:03.100,0:30:08.980
remdesivir, then go back free nucleotides[br]take rip out the remdesivir, throw it away

0:30:08.980,0:30:15.120
and get the proper nucleotide to build in.[br]So. We're hoping that one over pea-rel will

0:30:15.120,0:30:18.839
be better, which, by the way, uses a[br]similar mechanism. It's called a

0:30:18.839,0:30:31.870
nucleotide. Yeah, it's similar to a[br]nucleotide. Here's another arrow we found

0:30:31.870,0:30:35.070
in the bottom of the structure, only going[br]to show you because I think the software

0:30:35.070,0:30:40.150
by Tristan Kroll is so cool, it does a[br]real time molecular dynamics simulation

0:30:40.150,0:30:44.510
while you're dragging around your[br]structure. We found that there is an error

0:30:44.510,0:30:48.490
in the way the whole molecule was[br]arranged. If there's any specialist, there

0:30:48.490,0:30:52.100
was a nine amino acid out of reach[br]associate. OK, I'm going to stop like

0:30:52.100,0:30:56.490
geeking out. There was just an error. Let[br]me show you how he correct that. So first

0:30:56.490,0:31:00.990
you marks up the wrong region and then he[br]releases it and <i>quickly flying-away noise</i> it goes where it's up to

0:31:00.990,0:31:04.870
go. I wish my life would always be like[br]this, you said were free days glasses in

0:31:04.870,0:31:08.309
front of your computer. You need hours to[br]do this by hand, but his software just

0:31:08.309,0:31:15.360
does it. Sorry. It's just if you've spent[br]months doing this, you're totally excited

0:31:15.360,0:31:21.580
by this wobbly molecule. I just wanted to[br]show you because I think it's so cool. All

0:31:21.580,0:31:29.549
right. Back to a more general content. We[br]have an hour RNA and a let's imagine we

0:31:29.549,0:31:35.419
didn't get any like good drugs so far, so[br]the infection cycle is still ongoing. The

0:31:35.419,0:31:40.050
RNA now is exported from the endoplasmic[br]reticulum. By the time we make this, we

0:31:40.050,0:31:43.750
didn't know how. But Hamburg researchers[br]and Dutch researchers have now found out

0:31:43.750,0:31:49.370
how this actually works as a pore here and[br]the pore gets the RNA out. The RNA then

0:31:49.370,0:31:53.890
gets packed into new nucleocapsid[br]were also coded by the genome

0:31:53.890,0:31:59.760
of the virus, then gets wrapped into a new[br]double membrane, which is host membrane.

0:31:59.760,0:32:05.970
Just it has no spikes, which also were[br]produced from the genome. And then, of

0:32:05.970,0:32:11.580
course, due the Golgi apparatus is somehow[br]involved, it gets exported. Of course, for

0:32:11.580,0:32:17.850
everyone that infected a cell, there will[br]be thousands that are produced and that's

0:32:17.850,0:32:26.120
the entirety of the SarsCoV 2 viral[br]life cycle. I know, this was a little bit

0:32:26.120,0:32:31.740
much, but I think this is cool and[br]exciting and just about what, you know. I

0:32:31.740,0:32:36.980
hope the public can understand about this.[br]It hopefully also tells you why molecular

0:32:36.980,0:32:42.740
structures are important, so they let us[br]understand how the virus works, how host

0:32:42.740,0:32:48.481
cells are infected. They can help us to[br]find drug targets and to do structure

0:32:48.481,0:32:53.370
based drug design, where we find drugs[br]that specifically block these big

0:32:53.370,0:32:59.510
molecular machines from doing their work.[br]They also help us to understand the

0:32:59.510,0:33:06.549
structures of vaccines and antibodies, and[br]they also let us understand changes due to

0:33:06.549,0:33:10.850
two mutations, I haven't got an example[br]because of the time. But when we get a

0:33:10.850,0:33:16.010
mutation with the structure, I can kind of[br]tell you, that it is going to change or

0:33:16.010,0:33:21.341
that it is going to change only by knowing[br]the new genome. I can already make a

0:33:21.341,0:33:25.340
prediction about what the mutation is[br]going to change in a functionality. That's

0:33:25.340,0:33:31.850
really important. So in my group, we have[br]some theories what a Micron actually does.

0:33:31.850,0:33:36.340
We haven't published and we haven't even[br]tweeted about them yet because we're still

0:33:36.340,0:33:43.240
waiting for research results. But it's[br]important to understand these molecular

0:33:43.240,0:33:52.169
structures, however, is not very easy to[br]get them. So what are the problems? When we

0:33:52.169,0:33:58.750
do our measurement, we get density in this[br]case, the density is blue. It's from the

0:33:58.750,0:34:02.179
spike head that I've shown in the[br]beginning, right? So the top that you may

0:34:02.179,0:34:06.490
recognize, this looks a little bit like[br]the blue density here. This is the result

0:34:06.490,0:34:10.919
from our research. And in this case, I[br]have built almost all of the molecule

0:34:10.919,0:34:15.290
already, so I'm going to show it. This is[br]like the software. We're actually using a

0:34:15.290,0:34:19.659
tenfold to speed I'm usually using, and I[br]would usually be sitting there with 3D

0:34:19.659,0:34:24.190
glasses. So here's the density. I said[br]that with my 3D glasses and this bit

0:34:24.190,0:34:30.579
hasn't been built, so you can now see me[br]like by hand. And one bit of molecule

0:34:30.579,0:34:34.999
after the other trying to get the murder[br]ought to be, and you can quite well see

0:34:34.999,0:34:40.030
that the computer is not able to do it all[br]automatically. So I have to help it a

0:34:40.030,0:34:44.240
little bit. And as I said, it's about 10[br]times the speed. It's even got like the

0:34:44.240,0:34:49.179
warning from the bin program not reacting[br]all of the software, it's also not

0:34:49.179,0:34:53.800
commercial. This has been developed by[br]other scientists, so the usability is like

0:34:53.800,0:34:59.609
so-so cool, just an amazing program. But[br]if you want some new functionality, you

0:34:59.609,0:35:04.440
better program it yourself, because perhaps[br]no one else is going to do it. And we have

0:35:04.440,0:35:10.549
actually contributed with a plug in or two[br]to cut. Yeah, you can see it's not always

0:35:10.549,0:35:13.869
easy, so I try and go, like, now it's[br]good. Settings should nicely in the

0:35:13.869,0:35:21.890
density and here it's fairly easy. My[br]students love doing this is like for them.

0:35:21.890,0:35:25.099
It's like computer gaming. They do it for[br]three months straight. If you don't like,

0:35:25.099,0:35:30.450
get them off the chair, go right up your[br]physics. They'll do it forever. And

0:35:30.450,0:35:35.289
secretly, I'm jealous. Because I also like[br]doing this. I don't know if you can

0:35:35.289,0:35:45.499
follow, but this is like playing a game.[br]Away, if you're interested in playing this

0:35:45.499,0:35:54.010
game, we are also having. Like practical[br]places and stuff. Right! So building,

0:35:54.010,0:35:58.790
building, building, going like, oh,[br]there's another alanine, I need a pralines

0:35:58.790,0:36:03.609
or mutated it. I go like, Yeah, OK, now[br]it's all nicely sitting. So that was easy.

0:36:03.609,0:36:09.240
But what do I do here? So I've built for[br]something here. But is it correct? The

0:36:09.240,0:36:12.950
density does not really tell me what's[br]going on here, and I'm going to show it

0:36:12.950,0:36:18.680
this to you in slower again. So you[br]understand the problem, right? In this

0:36:18.680,0:36:22.720
then part of the density, I can really not[br]tell only from the density what's going

0:36:22.720,0:36:28.890
on. I know approximately what a molecule[br]must look like due to the sequence. So

0:36:28.890,0:36:31.740
I've got some information. I know which[br]Atom is connected to which, but how it all

0:36:31.740,0:36:37.119
three dimensionally fits in here, even if[br]I know which lines have to go in, there is

0:36:37.119,0:36:41.849
super hard. So it would be very easy for[br]me to make an error here, because the

0:36:41.849,0:36:45.979
measurement data don't tell me enough[br]about what the model actually should look

0:36:45.979,0:36:55.500
like and several interpretation., everal[br]models would all be possible. So this is

0:36:55.500,0:36:59.130
kind of difficult. I'm just seeing a[br]questionnaire that I may want to answer

0:36:59.130,0:37:03.670
right away. Within could is it possible to[br]verify if you have chosen created the

0:37:03.670,0:37:09.379
right building blocks, you know, the[br]building blocks because of the genome? So

0:37:09.379,0:37:14.539
Gene tells you the order of amino acids[br]you want to put after each other. So if

0:37:14.539,0:37:21.839
you started at the right point, the rest[br]will also be like the correct atoms and

0:37:21.839,0:37:26.039
the correct connection. But how it like[br]three dimensionally faults, you don't

0:37:26.039,0:37:36.600
know. You have to make that on the[br]density. So it is possible to do it. You

0:37:36.600,0:37:41.910
have to write building blocks at hand.[br]Usually if there are if there is like, you

0:37:41.910,0:37:46.160
know, if a magnesium ion, for example, is[br]sitting there, the magnesium ion was not

0:37:46.160,0:37:51.250
in your genomic information. You just need[br]to know what you're doing to recognize

0:37:51.250,0:37:58.190
this is a magnesium ion ore does this a[br]diophosphate or something like this?

0:37:58.190,0:38:06.490
Right. Going to answer the rest of the[br]questions later. Molecular models need to

0:38:06.490,0:38:11.049
be built by hand. This can lead to errors.[br]There a few automatic algorithms do work

0:38:11.049,0:38:17.059
under favorable circumstances, but most of[br]the stuff still has to happen by hand. As

0:38:17.059,0:38:21.549
of today, and I got my postdoc from like[br]holidays for 15 minutes today, and he gave

0:38:21.549,0:38:25.500
new numbers. So we've got 1909 [br]molecular structures

0:38:25.500,0:38:31.729
today. New structures come out every[br]Wednesday. There are 1334 from X-ray

0:38:31.729,0:38:36.109
crystallography. That's the thing. With[br]the particle accelerator in Hamburg, I

0:38:36.109,0:38:41.150
thought, they have been measured at[br]synchrotrons all over the world. Not only

0:38:41.150,0:38:46.079
Hamburg, where BioNTech structures have[br]been measured, but also had SARS. There

0:38:46.079,0:38:51.890
have been large screens a diamond in Japan[br]and China at Sesamia, at Solemy, in

0:38:51.890,0:38:57.349
America. Synchrotrons all over the world[br]contributed to this. 35 from nuclear

0:38:57.349,0:39:02.470
magnetic resonance, which is a little bit[br]of a niche method for this type of study.

0:39:02.470,0:39:08.579
And 566 from electron microscopy. [br]So 1909 molecular structures

0:39:08.579,0:39:16.339
of different states of 17[br]macromolecules, 17 proteins from a total

0:39:16.339,0:39:26.789
of 28. So corona virus in total has 28[br]different genes, 4 proteins. There are 28

0:39:26.789,0:39:33.079
proteins. And we only structurally know 17[br]of them. And then we have like different

0:39:33.079,0:39:37.119
versions of them, different ph, different[br]temperatures, spike, head bit of spike

0:39:37.119,0:39:47.259
head, spike head with antibody, things like[br]that. So a 1900 data sets that's in total.

0:39:47.259,0:39:51.980
Errors and structures, as we've[br]just seen, can happen because fit between

0:39:51.980,0:39:58.940
the data and model is bad, because complete[br]automation is not possible. Models are

0:39:58.940,0:40:04.819
built manually expertize in many different[br]areas needed. You need to be good

0:40:04.819,0:40:07.819
software. You need to have done all the[br]lab work. The measurement needs to be done

0:40:07.819,0:40:12.269
right. Processing needs to be made. You[br]need to know your statistical validation.

0:40:12.269,0:40:17.180
You need to know your chemistry. You need[br]to know your biology. So it's really not

0:40:17.180,0:40:22.230
easy and you need to know your 3D goggles[br]unless you get sick from them, in which

0:40:22.230,0:40:27.720
case you can't use them. One of the major[br]aspects of software, the methods you're

0:40:27.720,0:40:35.789
using and this is where we come in. Small[br]structural errors can lead to big

0:40:35.789,0:40:41.000
structural problems downstream. Imagine[br]the bid was to remdesivir, the diphosphate

0:40:41.000,0:40:45.979
there, the fact that there was something[br]bound into that structure that was not

0:40:45.979,0:40:51.769
really there. But the model had dose like[br]additional free magnesium ions down the

0:40:51.769,0:40:59.809
line, as I know from insiders, led to like[br]waste of hundreds thousands of dollars

0:40:59.809,0:41:05.299
and many hours of work time in drug[br]discovery because they kind of like fed

0:41:05.299,0:41:09.990
this model in order to find a drug that[br]ultimately never bound because of

0:41:09.990,0:41:17.680
magnesium ion wasn't actually there. So[br]if we make small structures, that builds

0:41:17.680,0:41:21.599
up hugely for the downstream applications[br]where they need these molecular

0:41:21.599,0:41:31.279
structures. Errors are common. And now we[br]add to this an ongoing pandemic. Right.

0:41:31.279,0:41:35.720
And her scientists are there to rescue[br]today. Lockdown happened, you're sitting

0:41:35.720,0:41:41.339
at home, there are no colleagues to help[br]you. Your child is home schooling. The dog

0:41:41.339,0:41:45.430
wants to be fed, your grandma calls,[br]because she's worried and you've got to

0:41:45.430,0:41:50.939
solve the spike structure on which lives[br]will depend as fast as possible. Normally,

0:41:50.939,0:41:54.450
we take a year to five to solve a[br]structure, and in the pandemic you only

0:41:54.450,0:42:03.940
got three months. Of course, errors are[br]going to happen. So that's well, just a

0:42:03.940,0:42:08.779
matter of fact. We've got to arrange[br]ourselves with it. It's not the fault of

0:42:08.779,0:42:14.170
individuals, it's how the whole thing[br]works. It's such a complex process. Errors

0:42:14.170,0:42:19.539
are going to happen! Now in normal life my[br]team and I methods developers and

0:42:19.539,0:42:24.589
structural biology. We are the people, who[br]give us the experimental techniques and

0:42:24.589,0:42:30.670
software to solve their structures as best[br]as we and they can. We're not usually in

0:42:30.670,0:42:36.569
the in the stage like we're usually, you[br]know. For every Nobel Prize, there have

0:42:36.569,0:42:41.109
been like dozens of Nobel Prizes in[br]structural biology has been methods

0:42:41.109,0:42:45.059
developed in the background to develop the[br]methods that made it possible to see, you

0:42:45.059,0:42:49.299
know, the structure of the DNA double[br]helix or structure of the ribosome, or the

0:42:49.299,0:42:56.029
structure of the influenza virus. It's[br]just that normally we're just enablers.

0:42:56.029,0:43:05.130
However, here was the pandemic and very[br]many structures that had errors. So we did

0:43:05.130,0:43:10.509
what we needed to do. We came together as[br]a relatively large team under my

0:43:10.509,0:43:17.279
leadership, we are today 23 people, we[br]peaked at 27 last year from nine countries

0:43:17.279,0:43:21.009
to check an improve the molecular[br]structures of SARS-CoV-1 and SARS-CoV-2.

0:43:21.009,0:43:31.369
So. We are methods developers, most of are[br]methods developers, we are specialists in

0:43:31.369,0:43:36.441
solving structures. We evaluate all the[br]published Structures and Protein Data

0:43:36.441,0:43:43.619
Databank or PDB from SARS and SARS-[br]CoV-2. We reprocess all of them and we

0:43:43.619,0:43:49.549
remodel them, although not all are looked[br]at manually, because that would be just

0:43:49.549,0:43:53.309
too much. We also do a scientific[br]dissemination, putting these structures

0:43:53.309,0:43:58.430
into context for people who want to start[br]doing molecular research on corona virus.

0:43:58.430,0:44:04.680
And we do public outreach. I'll give you a[br]quick insight into our pipeline because I

0:44:04.680,0:44:10.039
thought the software might be interesting[br]for you. So every Wednesday come new

0:44:10.039,0:44:14.529
entries of molecules in the protein[br]databank, which is, by the way, the World

0:44:14.529,0:44:19.039
Wide Protein Databank is an open, open[br]resource. Everyone in the world can

0:44:19.039,0:44:23.470
download the new structures, and all the[br]journals require people who make new

0:44:23.470,0:44:28.099
structures to put them there, which is[br]nice. I'm really privileged to be in a

0:44:28.099,0:44:33.150
field where the data are public. We[br]compared the new structures with the NCBI

0:44:33.150,0:44:37.950
proteomics, so the genes from corona virus[br]to find the structures that belong to

0:44:37.950,0:44:44.109
corona virus, put everything into an sql[br]metha database. Then we calculate how

0:44:44.109,0:44:48.529
different the structures are from the ones[br]we already know. We look whether all

0:44:48.529,0:44:52.480
measurement data available, so we have a[br]big problem of not all measurement data

0:44:52.480,0:44:58.640
being published. I hope we are going to be[br]like astronomy one day, where everything

0:44:58.640,0:45:06.440
gets published. I am sitting in the some[br]German cometies to that end STIKO AM which

0:45:06.440,0:45:11.059
is a very new hub. And then we run a[br]number of specialized programs which all

0:45:11.059,0:45:16.349
do validation and put the results on[br]GitHub immediately. On Thursday, at the

0:45:16.349,0:45:22.160
latest, researchers can find our elevation,[br]remodeling and the quality indication for

0:45:22.160,0:45:28.770
the structure everything, that can be done[br]automatically online. We then, for some

0:45:28.770,0:45:33.970
structures, manually rebuilt them, so we[br]actively look weathered our problems, that

0:45:33.970,0:45:38.200
was, for example, the case with the[br]remdesivir structure. We tried to do this

0:45:38.200,0:45:42.500
for those structures that we think drug[br]designers will use the most or that are

0:45:42.500,0:45:47.910
really important. And when we find errors,[br]we contact our original office first and

0:45:47.910,0:45:55.119
tell them we found an error here is the[br]corrected structure. Use our data, you

0:45:55.119,0:46:00.929
don't need to cite us, just correct your[br]structure in the database, please. This

0:46:00.929,0:46:05.269
means we won't get credit, but I meant[br]that at the beginning of the pandemic,

0:46:05.269,0:46:11.279
people were adjusting their structures[br]already when the preprint was out, so

0:46:11.279,0:46:15.420
there would not be problems downstream.[br]And I have often been asked I would like

0:46:15.420,0:46:20.789
to like this again. That was really like[br]why people accepted our corrections,

0:46:20.789,0:46:25.539
because they didn't need to give anyone[br]credit. They could just like change them.

0:46:25.539,0:46:30.230
And the database is also online, so[br]everyone from the Philippines to the U.S.

0:46:30.230,0:46:34.940
can just use them, whether it's like a[br]commercial person or a taxpayer, or a

0:46:34.940,0:46:40.559
private person research institution, a[br]foundation, everyone can use our data.

0:46:40.559,0:46:44.309
They're just online there for everyone,[br]and we only ask them to give us credit in

0:46:44.309,0:46:51.109
the form of a reference citation. We[br]disseminate the data via GitHub via

0:46:51.109,0:46:57.190
Twitter. 3D bio notes, which is a three[br]dimensional database linking directly into

0:46:57.190,0:47:06.640
our database, we contact the offers. We[br]also have entries in Proteopedia. Molprobity,

0:47:06.640,0:47:11.450
which is a virtual bioinformatics[br]institute, links directly into our

0:47:11.450,0:47:15.100
database. So they're always like up to[br]date showing what we are doing. We have a

0:47:15.100,0:47:20.440
homepage and we do reviews. There's a lot[br]of downstream users. The biggest ones are

0:47:20.440,0:47:29.309
the EU Jedi Grand Challenge folding at[br]home, which peaked out in July last year.

0:47:29.309,0:47:36.809
I think a 2.4 xTFLOPs computing power for[br]molecular simulations and used in the

0:47:36.809,0:47:43.830
majority our models to start from. And[br]also very big is IBM open pandemics. But

0:47:43.830,0:47:47.989
there are a number of others, plus many[br]individual apps. So we found a great new

0:47:47.989,0:47:55.469
many friends. Here is our homepage, that's[br]where you can find it. There's also an

0:47:55.469,0:48:01.489
English version, you can find blog posts[br]for the public and for scientists. And in

0:48:01.489,0:48:07.020
the end, I would like to talk for like[br]five minutes about daily life in ritual

0:48:07.020,0:48:14.529
mobility. So my team is over 20 people[br]from nine to ... we cover nine time zones,

0:48:14.529,0:48:21.520
right? Where nine hours time shift apart.[br]And we had several lockdowns. So.

0:48:21.520,0:48:26.839
Actually, the majority of people in the[br]task force, about half of them don't work

0:48:26.839,0:48:31.580
for me. They are volunteering their[br]researchers elsewhere that volunteer to be

0:48:31.580,0:48:36.349
a part of this effort. And there are many[br]people in the task force who have never

0:48:36.349,0:48:43.989
like personally met. So how do you make[br]group coherence if you are working for 20

0:48:43.989,0:48:49.450
months or 22 months by now in an[br]environment like this, right? We founded

0:48:49.450,0:48:56.020
ourselves in March 2020 as a chat group[br]called the Coronavirus Structural Task

0:48:56.020,0:49:02.839
Force, which was a job back then. It[br]didn't remain a joke. But that's how life

0:49:02.839,0:49:08.400
plays. We have everyday Zoom meetings at[br]10 o'clock, one time per week in the

0:49:08.400,0:49:14.700
afternoon. So do people from Oregon can[br]join us. We do a lot of like media

0:49:14.700,0:49:20.440
outreach in international and German[br]media. We've been like on nano and Terra X

0:49:20.440,0:49:24.599
and Planet E, we've been in breakfast[br]television. That was a particularly

0:49:24.599,0:49:30.069
interesting experience. My email got link[br]to Querdenker and I got a few very

0:49:30.069,0:49:34.579
interesting email exchanges. I also must[br]say I never got insulted or frightened by

0:49:34.579,0:49:41.589
anyone, so I just discussed with them and[br]it worked out. And I'm happy because like

0:49:41.589,0:49:49.410
I understood, like how, what the theories[br]are, and that was very interesting. Keep

0:49:49.410,0:49:53.680
the media also like to write about my[br]hair, my eyes, blah blah blah on these

0:49:53.680,0:49:58.440
things. I just want to note that Streeck[br]is about my age, and Drosten is only nine

0:49:58.440,0:50:05.980
years older than me. So really? OK,[br]whatever. Most importantly, they're

0:50:05.980,0:50:11.300
talking about our research. We also did a[br]lot of social media. I got a Twitter

0:50:11.300,0:50:15.880
account. Everyone else did as well. You[br]can watch us work on Twitch if you're

0:50:15.880,0:50:18.930
interested. We found that people find it[br]soothing to see us modeling these

0:50:18.930,0:50:23.519
structures. I was requested to make[br]stickers for the team as soon as we got a

0:50:23.519,0:50:28.719
grant and we got funded by the Federal[br]Ministry for Research and Education in

0:50:28.719,0:50:34.130
2020. We have a YouTube channel where you[br]can, for example, see the entry animation

0:50:34.130,0:50:40.510
and the students brought a cactus, which[br]is called Corina the Corona Cactus. I

0:50:40.510,0:50:47.470
know. It looked like we had fun, and we[br]did. I can tell you being caught, you

0:50:47.470,0:50:55.119
know, being at home, having to care for[br]your children. Having people dying. Having

0:50:55.119,0:50:59.880
an ongoing pandemic, knowing that I 'd be[br]more open pandemics is going to spend

0:50:59.880,0:51:04.589
another million based on your research.[br]And also that ZDF wants to talk to you and

0:51:04.589,0:51:09.981
the Berliner Abendblatt. This is so[br]stressful! Think about all the

0:51:09.981,0:51:15.349
responsibility we had, and it was really[br]terrible for us, so we needed to cheer up

0:51:15.349,0:51:19.999
every here and then, the whole group kind[br]of like grew together and we all became

0:51:19.999,0:51:25.999
friends. This was unheard. For us, it was[br]very uncommon as researchers. Typically,

0:51:25.999,0:51:29.029
our behavior with each other is much more[br]formal than their behavior and this group

0:51:29.029,0:51:35.880
was. But these were like exceptional[br]times, and we wanted to fight the pandemic

0:51:35.880,0:51:40.640
and inform the public. That's what we were[br]there for and was not so much about

0:51:40.640,0:51:49.340
personal gain. And that was nice. We have[br]a group chat. You know, I mean, I'm

0:51:49.340,0:51:53.289
talking to right audience, right? We have[br]a group chat. Do you know what that looks

0:51:53.289,0:51:57.759
like? Let me tell you. Typically,[br]professors don't communicate with this.

0:51:57.759,0:52:05.869
We have a virtual, Oh, we have a[br]virtual space. We hope to change to work

0:52:05.869,0:52:13.130
adventure soon. We all want to play games[br]in the evening occasionally with the

0:52:13.130,0:52:17.960
group, so we do some team building[br]efforts. When people can meet in person,

0:52:17.960,0:52:22.540
they usually do and sometimes they go and[br]travel and like, meet each other. But this

0:52:22.540,0:52:31.079
has been very limited. And we did grow[br]together as a network, that will be there

0:52:31.079,0:52:37.390
after the pandemic, so we are 25 people[br]all over the planet that did this

0:52:37.390,0:52:43.980
together. And even if we wouldn't have[br]made any difference against the virus, I

0:52:43.980,0:52:49.890
would still be happy to have done it for[br]the friendships I made. However, we did

0:52:49.890,0:52:54.910
make a dent. We don't quite know how big[br]it is because our science was open science

0:52:54.910,0:53:00.509
and the results could be gotten by[br]everyone without reference. But we know a

0:53:00.509,0:53:07.700
few things wouldn't have happened without[br]us. And I'm. Deeply grateful for having

0:53:07.700,0:53:17.739
had a purpose during this pandemic. In the[br]end, I have a little bit of a more serious

0:53:17.739,0:53:27.099
topic. My contract is going to run out in[br]May. I think it's going to be prolonged.

0:53:27.099,0:53:35.630
When it will, I'll be signing my 14 work[br]contract since 2008. 14, like I had 13

0:53:35.630,0:53:43.619
year contracts already out of all my task[br]force members, there is only one holding a

0:53:43.619,0:53:50.849
permanent position and two which are[br]retired. Everyone else, including six

0:53:50.849,0:53:56.990
people whose contract is going to run out[br]next year, are on temporary contracts and

0:53:56.990,0:54:02.140
not students. Students are extra. That the[br]students are on time limited contracts is

0:54:02.140,0:54:08.380
OK, but Germany's got a problem. 84[br]percent of academics in German

0:54:08.380,0:54:17.529
universities are on time limited[br]contracts. So are we. Only one task force

0:54:17.529,0:54:22.779
member has was a permanent position[br]signed, and that's not me. And this is not

0:54:22.779,0:54:27.440
so much on my behalf, because I'm going to[br]find my way through life. Look at all the

0:54:27.440,0:54:32.380
exposure I had, but there are people out[br]there who are single moms and dads, who

0:54:32.380,0:54:36.769
come from less privileged backgrounds or[br]had a harder life and who can just not

0:54:36.769,0:54:44.740
afford to be on one year contracts all the[br]time while holding a Ph.D.. We're losing

0:54:44.740,0:54:48.920
all these bright people and I'm seeing[br]them right. They leave my institute and

0:54:48.920,0:54:52.759
they go to industry. And then the[br]universities complain that they're not

0:54:52.759,0:55:00.700
competitive. We need to change the system.[br]We need to have more permanent positions

0:55:00.700,0:55:07.309
in science. I promise we won't perform[br]worse, if you give us permanent contracts.

0:55:07.309,0:55:16.989
We love what we are doing. So back to the[br]corona topic. In order to understand the

0:55:16.989,0:55:22.029
virus and its life cycle, we need to[br]understand its molecular biology. This

0:55:22.029,0:55:27.759
will help with the design of therapeutics.[br]We evaluated these molecular structures

0:55:27.759,0:55:32.869
with a bespoke pipeline, an expert[br]knowledge provided context and reached out

0:55:32.869,0:55:37.969
to the taxpayer and the general public to[br]inform them. We also wrote a paper

0:55:37.969,0:55:43.400
together with long off a list making the[br]invisible enemy visible, which is our

0:55:43.400,0:55:49.129
motto. And as we started this all with[br]questions, I'm going to end with

0:55:49.129,0:55:55.239
questions. Structural biology remains[br]difficult. What can we learn from our

0:55:55.239,0:56:01.499
findings? Should we, as a scientists[br]community, change our attitudes towards

0:56:01.499,0:56:10.640
errors? Should this serve as a model for[br]other projects, cannot serve as a model

0:56:10.640,0:56:14.400
for other projects? I hadn't thought about[br]this, but a nature editor asked me when I

0:56:14.400,0:56:18.809
was writing a comment whether we believe[br]that science should always be like this?

0:56:18.809,0:56:23.459
My God, that would be awesome. I would[br]totally be up for it if science would

0:56:23.459,0:56:27.009
always be like this! Come together with a[br]bunch of friends, but without funding!

0:56:27.009,0:56:32.210
Start doing something to, you know, fight[br]a global pandemic, then get some funding.

0:56:32.210,0:56:39.489
Still, having like no senior people on a[br]project. Can open science compete? I don't

0:56:39.489,0:56:49.099
know. We get pretty little credit. It[br]would, definitely. OK, science compete. I

0:56:49.099,0:56:53.289
don't know, it doesn't quite look like it[br]still getting measured only by the

0:56:53.289,0:56:58.979
citations my paper gets. And well, at[br]least a paper is not behind a paywall, but

0:56:58.979,0:57:02.799
if we would have published all our stuff[br]in like papers would possibly get more

0:57:02.799,0:57:09.369
credit. I really don't know, but we need[br]to work on this. If we want science, we

0:57:09.369,0:57:16.700
need to change how people are rewarded.[br]How senior they really need to be. I'm 39.

0:57:16.700,0:57:22.200
It seems I'm called a junior group leader.[br]All of us are young. The youngest is 24.

0:57:22.200,0:57:26.859
He's writing our first Alpha article about[br]a corona virus protein. I feel that the

0:57:26.859,0:57:31.259
German academic system and all over the[br]world, actually you need to be older and

0:57:31.259,0:57:37.119
older to become a professor and be[br]permanent and be like a grant holder. I

0:57:37.119,0:57:41.180
don't think it's necessary, I think that[br]professors could be 30 and the world

0:57:41.180,0:57:49.030
wouldn't, you know, like, go down. Well,[br]what will change in science after a

0:57:49.030,0:57:54.289
pandemic? We had like large exposure. It[br]certainly will also have to do with like

0:57:54.289,0:57:58.580
questions like did the virus now come from[br]an app or didn't it? That, you know, would

0:57:58.580,0:58:03.720
change how people view science, I'm sure.[br]How will scientists be viewed by the

0:58:03.720,0:58:08.960
public? Right. Right now, of course, you[br]know, mom and dad are very proud, but.

0:58:08.960,0:58:14.119
What's going to change? Are we going to[br]still be the bad guys because we often

0:58:14.119,0:58:19.180
are. But I'm like general, exclusively[br]taxpayer funded. I never took any money

0:58:19.180,0:58:23.519
from the pharmaceutical industry. I have[br]like, you know, no stakes in this game.

0:58:23.519,0:58:31.959
I'm just like earning tax money, so I[br]feel that, there is a whole complex of

0:58:31.959,0:58:35.420
difficult things there, how people regard[br]science, but definitely the pandemic is

0:58:35.420,0:58:40.079
going to change, how science is going to[br]be viewed. What's that going to be?

0:58:40.079,0:58:48.400
<i>Exspiration</i> In the end. I'd like to[br]thank all the task force members and all

0:58:48.400,0:58:54.000
our collaboration partners and our[br]scientific fairy godmother, Alvin Pearson,

0:58:54.000,0:58:59.099
who had little role in this research but[br]much role in our mentorship and bringing

0:58:59.099,0:59:04.299
us forward. My home, the University of[br]Hamburg, the Coronavirus Structural

0:59:04.299,0:59:08.499
Taskforce, our we are funded by the[br]Deutsches Officials Command Trust and the

0:59:08.499,0:59:13.699
Federal Ministry for Research and[br]Education. I would like to point out that

0:59:13.699,0:59:19.130
we are looking for student assistance, not[br]only for scientific work, but also for

0:59:19.130,0:59:25.430
social media video and programing work and[br]3D printing. So if you know anyone who's

0:59:25.430,0:59:30.710
interested, please point him in my[br]direction. My email is there. We are also

0:59:30.710,0:59:36.219
offering Bachelor, Master and Ph.D. thesis[br]in areas that cover both Lab work and

0:59:36.219,0:59:43.691
computer work, which is a rare thing these[br]days. You can find us on YouTube and the

0:59:43.691,0:59:50.990
internet and on Twitter and. I'm looking[br]forward to the discussion. And thanks for

0:59:50.990,0:59:53.549
listening.[br]melzai_a: You write it, so.<i>laughing</i>

0:59:53.549,0:59:57.660
Andrea: I just brought it up, must have[br]bmbF because I'm now sitting on the screen

0:59:57.660,1:00:01.519
on dislike committees more and more, I'm[br]reaching an age where I'm sitting on

1:00:01.519,1:00:05.359
committees and I told them legacy software[br]is a problem.

1:00:05.359,1:00:07.900
melzai_a: It's a real.big problem.[br]Andrea: You know, it's very troubling that

1:00:07.900,1:00:12.829
the software is written in Fortran. Not[br]every second Linus go to, so it's written

1:00:12.829,1:00:17.930
like assembler. No one knows what's in[br]there anymore. And if a person dies, we're

1:00:17.930,1:00:21.530
not going to be able to do anything about[br]the algorithms. They're just going to be

1:00:21.530,1:00:24.810
lost.[br]melzai_a: Exactly. And they are. So you

1:00:24.810,1:00:28.459
have to first influence to grant writing[br]institutes that there are grants out so

1:00:28.459,1:00:32.849
that this software can read is reversed.[br]And this software is not easy. So that's

1:00:32.849,1:00:36.650
not your typical web page, so you need to[br]work together in such groups. And so it's

1:00:36.650,1:00:41.720
a very interesting piece of the problem, I[br]have to say. So sadly, as a PhD student went,

1:00:41.720,1:00:45.629
we weren't we were looking into this for[br]the second. Ah.. This is too big of a cake

1:00:45.629,1:00:49.990
to eat. <i>laughing</i> It was very[br]interesting. So I can also this and you

1:00:49.990,1:00:53.630
let you do it. The nudel tool suite, and[br]that's also only maintained by, I think,

1:00:53.630,1:01:00.739
three people also. So even that one, it's[br]with many more. It's still not good. So

1:01:00.739,1:01:05.900
just my sense of that one.[br]Andrea: So I brought my Ph.D. thesis. I

1:01:05.900,1:01:08.329
worked on chalex?? and that faces similar[br]problems.

1:01:08.329,1:01:15.319
melzai_a: Yeah, it's it's just used in the[br]entire world to solve every small molecule

1:01:15.319,1:01:20.359
structure. There is more or less it was[br]like, Yeah, so questions were the

1:01:20.359,1:01:25.440
questions. Frankly, we ain't got a first[br]question, I think around 20 or 30 minutes

1:01:25.440,1:01:30.269
ago, if we yeah, that's that's why that[br]was so great as a signal angel, she's

1:01:30.269,1:01:34.969
picking up all of these points. And so the[br]first question was how do the virus

1:01:34.969,1:01:37.400
variants affect the shape or form of the[br]virus?

1:01:37.400,1:01:44.329
Andrea: I think they so no matter like,[br]OK, this is the old model as we know, then

1:01:44.329,1:01:48.690
there should be fewer spikes and should be[br]a bit smaller. But nothing would change on

1:01:48.690,1:01:54.920
this view, like the scale is way too[br]large. The mutations each change about 10

1:01:54.920,1:02:01.099
atoms, so every like amino acid at this[br]different, it's about 10 atoms. And those

1:02:01.099,1:02:06.420
changes would be so small you could not[br]see them on the virus model. You'd

1:02:06.420,1:02:10.239
actually need to look at the head of the[br]spike in order to see the mutation and

1:02:10.239,1:02:16.079
what it actually does. So the changes are[br]too small to show them in the model. That

1:02:16.079,1:02:20.499
doesn't mean they're not meaningful. So as[br]you've seen, like the head of the spike

1:02:20.499,1:02:28.079
binds to the host, to the host cell, to[br]ACE2 receptor, and that binding is highly

1:02:28.079,1:02:35.920
influenced by this by the mutations. Now[br]we found that we may end up lucky because

1:02:35.920,1:02:41.729
the same paths were to antibody as binding[br]is also the piece that binds to the host

1:02:41.729,1:02:47.380
cell. So everything that would mate[br]despite change in a way that the antibody

1:02:47.380,1:02:55.170
couldn't bind any more to it. For its head[br]would have also changed how it bound to

1:02:55.170,1:03:03.000
the host cell. However, it seems that[br]Omicron is still able to bind human cells

1:03:03.000,1:03:08.780
very efficiently, while antibodies cannot[br]recognize it so easily. That may have to

1:03:08.780,1:03:13.099
do with like this finger's actually like[br]packed and you could imagine like putting

1:03:13.099,1:03:17.999
cotton wool around it. That's called[br]glycosylation. It's got long sugar changes

1:03:17.999,1:03:22.840
that are rule, and they're there to[br]obscure the immune system, like the

1:03:22.840,1:03:27.530
antibody goes like orders, wool. I can't[br]really find where I'm on to bind. Is it

1:03:27.530,1:03:34.210
here? I don't know. And that's changed in[br]Omicron, but it's not fully understand

1:03:34.210,1:03:40.519
yet. I saw there was a new structure this[br]week, but I haven't looked at it yet.

1:03:40.519,1:03:44.529
However, the changes are too small to show[br]it in the virus model. They're like really

1:03:44.529,1:03:50.819
tiny changes. And another change that[br]happens in Omicron as well is the

1:03:50.819,1:03:56.799
proofreading mechanism. When the RNA is[br]copied is like damaged and we think it's

1:03:56.799,1:04:01.869
damaged. So their so-called eNd RNA, which[br]is a proofreading protein, its sharp is

1:04:01.869,1:04:06.630
like to go like a star and correct? Yes,[br]correct, correct. Correct. That seems to

1:04:06.630,1:04:10.959
be a little bit broken. So it could be[br]that Omicron is accumulating so many

1:04:10.959,1:04:17.229
mutations because it's RNA copy machine.[br]It's like not working as it should is

1:04:17.229,1:04:21.630
basically not proofreading. That would[br]mean that more viruses are produced that

1:04:21.630,1:04:26.549
are not viable and cannot survive. But it[br]would also mean that it mutates much

1:04:26.549,1:04:32.009
faster, and we think that may have an[br]influence. But that's just theory. So far

1:04:32.009,1:04:36.799
this hypothesis, we haven't proven it yet.[br]So this is why I haven't tweeted about it

1:04:36.799,1:04:42.059
yet, because it's just a theory, but it[br]would make sense, right?

1:04:42.059,1:04:46.400
melzai_a: Connected to that, I would have[br]a question the ice receptor of small children

1:04:46.400,1:04:51.339
is a little bit different than that one[br]of the adults to you do know about that

1:04:51.339,1:04:56.049
because all the concern to what's more,[br]the smaller children are the defense.

1:04:56.049,1:05:01.499
Andrea: I can't. I have read that, but I[br]haven't looked into it properly. So I'm

1:05:01.499,1:05:06.249
I'm afraid I'm not going to answer this[br]question because I feel I would rather not

1:05:06.249,1:05:08.319
say anything about it than say something[br]that's wrong especially.

1:05:08.319,1:05:11.839
melzai_a: Well. We're looking forward to[br]the secretary's right in the public PDB so

1:05:11.839,1:05:19.099
that everybody can look at them and.[br]Andrea: Know we live in an age of

1:05:19.099,1:05:23.079
preprint, and very often the PDB papers[br]are there when a preprint comes out, which

1:05:23.079,1:05:28.079
is how we called so many errors, right?[br]They published a preprint, they put out a

1:05:28.079,1:05:32.349
structure. We went like, there's errors in[br]the structures. And then when they

1:05:32.349,1:05:34.880
published actual paper, everything was[br]corrected.

1:05:34.880,1:05:39.380
melzai_a: And she's agreed that believe[br]the changes, I think are checked on the

1:05:39.380,1:05:42.619
PDB.[br]melzai_a: This is, in fact, because yes,

1:05:42.619,1:05:45.799
that's that's what IT people like[br]because then that, you know, there's a

1:05:45.799,1:05:52.079
history is very important. And there's a[br]second question and it goes towards the

1:05:52.079,1:05:54.119
tools that I use to simulate those[br]molecules.

1:05:54.119,1:05:59.359
Andrea: Wait, wait, wait, wait. I have a[br]follow up to this: thing that I would

1:05:59.359,1:06:03.890
really like to see, but it hasn't happened[br]yet. The PDB is a very static repository

1:06:03.890,1:06:09.229
where only original offers are allowed to[br]change their structures. Now, imagine if

1:06:09.229,1:06:14.859
the protein data bank would be like GitHub[br]with pull requests. We could go like, go

1:06:14.859,1:06:18.789
like, changed the molecule around. Go[br]like, no, it's a better fit to your data.

1:06:18.789,1:06:22.979
Please pull.[br]Herald: That would be a very subversive

1:06:22.979,1:06:26.259
proposition. I would say.[br]Andrea: Yeah, wouldn't that be nice? I'm

1:06:26.259,1:06:31.319
like, Why aren't we doing this? It's like[br]the system is already there. It happens

1:06:31.319,1:06:35.769
that we have like repositories for a while[br]in software development. We could do the

1:06:35.769,1:06:44.049
same thing with models fitted to our[br]experimental data. But I think I need to

1:06:44.049,1:06:47.999
go into more committees.[br]melzai_a: Yeah, it sounds like this. I

1:06:47.999,1:06:53.839
would agree for that proposal. There was a[br]person that was asking about the toolsset

1:06:53.839,1:06:58.539
that you would use to simulate those[br]molecules and structures and so on. And if

1:06:58.539,1:07:03.599
you then create these more usable pictures[br]for the public, how do you balance

1:07:03.599,1:07:08.449
artist's impression simplified models and while keeping the scientific truth as

1:07:08.449,1:07:14.160
much as well as possible.[br]Andrea: The question you don't need the

1:07:14.160,1:07:17.719
public even to have this problem. You have[br]it already when you make pictures

1:07:17.719,1:07:21.589
scientifically. Because sometimes you want[br]to show our certain aspects of a molecule

1:07:21.589,1:07:26.630
very clearly, which means you have to cut[br]away, for example, a part of the molecule.

1:07:26.630,1:07:30.979
So one answer to this is the program that[br]does. The modeling is not a program that

1:07:30.979,1:07:35.329
you use to make the pictures. That's the[br]first thing you do. So you make your model

1:07:35.329,1:07:38.809
with one program and then you take all the[br]coordinates of the atoms and you throw

1:07:38.809,1:07:44.569
them into a professional rendering program[br]that like, we'll do it all pretty. But you

1:07:44.569,1:07:48.930
still have to make an executive decision[br]on what to show in your graphics, in your

1:07:48.930,1:07:56.799
paper. And I think that in particular,[br]structural biologists, who deal with three

1:07:56.799,1:08:01.329
dimensional and two-dimensional pictures,[br]we would do very well to think a lot more

1:08:01.329,1:08:07.769
about scientific illustration. So all my[br]team likes thinking about these things,

1:08:07.769,1:08:12.460
which is, I think, how we got where we are[br]now, right? They actually like stuff like

1:08:12.460,1:08:17.890
this. They go like, Oh, we can print it 3D[br]and we can put a magnet on it and it's

1:08:17.890,1:08:21.980
going to stick. But it turns out that[br]scientists also need these tools to

1:08:21.980,1:08:26.830
understand what's going on. It's like[br]actually having a 3D model helps you so

1:08:26.830,1:08:32.420
much with thinking about things. Crick and[br]Watson. They build a model of their DNA in

1:08:32.420,1:08:37.160
metal for a reason. Because we're looking[br]at three dimensional things, making them

1:08:37.160,1:08:43.560
like understandable with our hands. So[br]yes, as a good researcher, you're not only

1:08:43.560,1:08:48.739
able to explain your research to the[br]cleaning woman, you should also be able to

1:08:48.739,1:08:53.290
visualize it properly. And it's part of[br]the art. If you are a structural biologist

1:08:53.290,1:08:58.310
and you're not able to make good pictures[br]of your molecules, you're not a good

1:08:58.310,1:09:02.239
structural biologist. End of story. You're[br]in the wrong discipline, you should have

1:09:02.239,1:09:05.359
possibly chosen something where you need[br]less graphics.

1:09:05.359,1:09:12.069
melzai_a: And I think one of your industry[br]does is actually a of biologist by

1:09:12.069,1:09:17.699
training. Right? I think you've got...[br]Andrea: Tomasello is a proper biologist.

1:09:17.699,1:09:25.589
Thomas Splettstössersplit shrews as a prop about like a[br]Ph.D. in bioinformatics and Janet Erosa,

1:09:25.589,1:09:32.569
and LiU are both scientists who are having[br]a group that only deals with illustration.

1:09:32.569,1:09:36.460
So it's actually in science. We have[br]several groups in the world and structural

1:09:36.460,1:09:41.690
biology who only do illustration as[br]science. So David Goodsell with his

1:09:41.690,1:09:48.179
watercolors, is very well known, but Janet[br]Erosa is another one. So actually making

1:09:48.179,1:09:54.880
these animations and pictures is so[br]complicated that television can't do it.

1:09:54.880,1:10:00.480
And the ZDF made a series of animations,[br]so they made very nice ones for Planet E

1:10:00.480,1:10:06.090
Rizzo and Nano with us. But then they[br]asked my expertize to make another

1:10:06.090,1:10:11.429
animation. And they only had like a call[br]with us, and they never came back and then

1:10:11.429,1:10:18.630
published a completely wrong animation of[br]the entire viral mechanism under my name.

1:10:18.630,1:10:24.690
And I'm still sad every time I see it[br]three times a day. Heute Journal shows a

1:10:24.690,1:10:29.469
wrong structure of the virus for which[br]they claim that I helped them make it, and

1:10:29.469,1:10:34.530
I wrote to them and told them, Your[br]depiction of the virus is wrong. I can

1:10:34.530,1:10:43.199
help you make a new one. But it seems that[br]it's 2. deutsche Fernsehen der heute Journal at least didn't

1:10:43.199,1:10:49.830
care on. I guess they think it's not[br]important enough, but I think with a

1:10:49.830,1:10:55.050
threat like this where we really cannot[br]see the virus, it is important to bring to

1:10:55.050,1:11:00.679
the public the best possible depiction we[br]can deliver. Sometimes, however, as I

1:11:00.679,1:11:05.010
said, you omit certain aspects, for[br]example, to show the effects of a mutation

1:11:05.010,1:11:12.619
yet only showed a side of the mutation.[br]You don't show all the atoms. But. That's

1:11:12.619,1:11:15.830
really an important part of what we are[br]doing. Like pointing out the important

1:11:15.830,1:11:18.130
bits of ...[br]melzai_a: Scientific information is so

1:11:18.130,1:11:23.900
important, I think we have one final[br]question, which I would say comes out

1:11:23.900,1:11:30.460
comes towards the direction of the immune[br]system. And the question would be can you

1:11:30.460,1:11:35.949
can you define vaccine on purpose so that[br]the immune system can forget how to

1:11:35.949,1:11:39.889
produce the antibodies after a defined[br]period of time? And I think the concern

1:11:39.889,1:11:48.670
here is about increasing your [br]financial gain in the crisis, for example.

1:11:48.670,1:11:55.540
So programed obsolescence, as both of[br]those mentioned. So you're a bit late. So

1:11:55.540,1:12:00.800
if you could keep it short, that would be[br]great. OK? Andrea: The quick answer is no,

1:12:00.800,1:12:08.480
that's not possible. You can make. You can[br]enhance how long vaccines and how much

1:12:08.480,1:12:13.929
immune response you get from a vaccine or[br]certain additives. But you can not, like

1:12:13.929,1:12:18.810
make them a definite time because[br]everybody is different. So even when you

1:12:18.810,1:12:21.840
get your booster shot, they say six[br]months, but you may need it after three

1:12:21.840,1:12:27.550
months or you may need it after 12[br]authorityto. It's very hard to tell. And

1:12:27.550,1:12:32.520
pharma industry does not have tools that[br]would allow them that, to my knowledge. So

1:12:32.520,1:12:38.690
I think that's not a risk.[br]melzai_a: I mean, it's it's a human

1:12:38.690,1:12:43.780
system, and so complex is the rocket to[br]the Moon. So.

1:12:43.780,1:12:46.860
Andrea: I think it's a it's a valid[br]concern. It's just technologically not

1:12:46.860,1:12:53.429
possible. Luckily, I guess. [br]melzai_a: The final and really last question, I think,

1:12:53.429,1:12:57.110
is where can somebody find the 3D models[br]out there?

1:12:57.110,1:13:01.780
Andrea: Oh, you can go to inside[br]Corona..de and find a blog post about a 3D

1:13:01.780,1:13:13.050
thing or you go to Thingy Reuss and you[br]look for inside corona. I can. Yeah. Yeah.

1:13:13.050,1:13:21.110
I just go to. I just put it in. Why not[br]that? That's our home page and then on

1:13:21.110,1:13:29.380
thingy worse. It's also called inside[br]corona. And you can also write me a

1:13:29.380,1:13:36.860
message on Twitter if you don't find it at[br]a turn up. And remember, we're going to

1:13:36.860,1:13:43.260
put out a new model soon in January, but[br]I'm still waiting for the final files and

1:13:43.260,1:13:49.840
holiday. So it will be a few more weeks.[br]melzai_a: So but that trend in January,

1:13:49.840,1:13:53.260
not in December 2008. Yeah, exactly. Or[br]printed?

1:13:53.260,1:13:59.960
Andrea: Yes. So thank you very much for[br]having me.

1:13:59.960,1:14:02.820
melzai_a: Yeah, it was good. Thank you.[br]And I think if they are no more questions.

1:14:02.820,1:14:08.280
Everybody. All right. Oh, you know how it[br]looks like? I think that's really

1:14:08.280,1:14:12.020
important. I think one and a half years[br]ago, I came across the first pictures was

1:14:12.020,1:14:17.710
like, This is how it looks like. Now I can[br]tell it to the people who who don't read

1:14:17.710,1:14:26.090
the scientific original papers because[br]they are so difficult to read. So. Yeah.

1:14:26.090,1:14:34.130
Good. You know. And thanks for being here[br]and looking forward to hearing and seeing

1:14:34.130,1:14:38.050
more and hopefully once this will be over.[br]I think

1:14:38.050,1:14:43.730
Andrea: I hope so too. Going back out of[br]the spotlight to being just a Methods

1:14:43.730,1:14:45.730
developer, that would be nice. [br]Herald: That would be nice, yes.

1:14:45.730,1:15:05.000
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