WEBVTT

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Herald: So, willkommen zusammen. Heute
Abend gibt es den Talk von Andrea über den

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"Corona Virus Structural Task Force". Ich
bin melzai_a Herald für die Session. Wir

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haben einen Signal Angel, Dia, sie wird
die Fragen sammeln, die in den Chat

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gestellt werden und am Ende gehen wir im
Vortrag über diese Fragen. So viel zum

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Ablauf. Der Vortrag wird aufgezeichnet.
Und ist danach nachträglich verfügbar auf

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Media.ccc.de irgendwann in den nächsten
Tagen oder Wochen. Und damit würde ich mich

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freuen, Andrea, du als
Nachwuchsruppenleiterin an der Uni

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Hamburg, du hast die letzten zwei Jahre
mit den Codona Virus beschäftigt, und

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daraus wunderbare Visualisierung gemacht.
Wie lief es denn ab und wie sieht Corona

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eigentlich aus?

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Andrea: Ja, vielen dank! Erstmal danke für
die Einladung. Und ja, genau darum geht es

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in dem Talk jetzt, was wir die "corona
virus structure task force" nennen. I'm

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going to give the presentation in English;
so that international listeners can also

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listen in. But you can ask your questions
in, well, any language anyone here speaks.

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I understand German, English and Japanese.
And I want to start with a quote by Marie

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Curie. I know the room Mary is not named
after Marie Curie, but she said something

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that is very true in this pandemic, which
is: "nothing in life, is to be feared,

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only to be understood. Now is the time to
understand more so that we may fear less."

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And indeed, this holds true for the corona
virus more than anything, because as you

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all know, you cannot see the virus. You
can only see it indirectly visualized by

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science or you can see the measures against
it or you can see ill people. But the

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virus itself is invisible. And I'm going
to start this talk with questions. There

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will be many questions. And the first one
is, what does the corona virus look like?

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Now you may think, you know, but the
reality of it is that even German news has

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no idea. And I know that ZDF is now using
a different picture, which looks more

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similar to what I'm going to show, but
it's very wrong as well. This picture? Is

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what most people think the virus looks
like. And I also brought you like two top

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model and models of the virus. One can
even make sounds. Any spiky ball of

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this days really passes as a corona virus
because no one seems to know what the

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thing really looks like. Only it's like
crowned. And it has spikes. That's the

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only thing that all the models have in
common. But some things look like you can

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just, you know, like they are little Shrek
ears type things or have tentacles. No

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one really knows. So how do we know as
scientists and can viruses, be seen? If we

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imagine so, this is an electron
microscopic picture of a human hair. It's

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0.1 millimeters. It's the length of this
line, so the hair is a little bit less.

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The little red dot, which you may or may
not be able to see inside that circle is

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the size of the corona virus. Now if we
zoom into the picture of the hair, you can

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see, I hope, a little red dot here. And
that's the corona virus to measure. So it

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is 150 nanometers, or 0.0001.5 mm large. That is tiny

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even by scientists sentence. However. Even
smaller than the virus with 150

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nanometers. It's a single atom,
which is represented here again by a

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dot, which is barely visible and is 0.1
nanometers in diameter or one. Angstrom.

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Atoms are tiny, even compared to the
virus. A virus is composed being matter of

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very, very many atoms. How can we
visualize something this small? Can we see

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it with a light microscope? And what color
would the virus be? This is to scale.

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Yellow light. It is 600 nanometer
wavelength meaning from this point to

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this, it is 600 nanometers. So the
wavelength of visible light, which ranges

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from 400 to 780 nano meters, is actually
longer than the virus is white. So there

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is no chance whatsoever to ever observe a
single virus with light just physically

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not possible. We need something that has a
smaller wavelength, and there are two

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things we use X-rays, which have 0.1 nanometer wavelength. So they

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are very, very small. They're like light. They're also photons. We call it

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also X-ray light (Röntgenstralung,
Röntgenlicht). But they have so high energy

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that their wavelengths are tiny. The other
thing are electrons, which have even

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smaller wavelengths. If you choose to
regard them not as particles, but as

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waves. So we can use electrons and X-rays
to observe the virus, and we do. And for

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this, we have several possibilities. One
of them is large particle accelerators

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like the one I'm working on in Hamburg,
which produces very intense X-rays.

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Another one is an electron microscope. So
here is a model of an electron microscope.

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In order to use it, you need a scientist
and then you shoot an electron beam from

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an electron cannon. That's the official
scientific term. It's an electron cannon

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onto both an electron gun electron cannon
electron gun. You shoot your electrons

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through lenses, which are magnetic.
Electrons are negatively charged so the

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magnetic field can be used as a lens
system onto a sample. For example, the

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virus and then you have a detector. What
do we see on this detector? We should

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viruses with electrons and record how many
electrons pass through the sample? What we

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see looks like this. So of course, it's
black and white because electrons come.

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There's no colors involved. And what you
can see is a dark shadow. And then around

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it, a little bit of bright spots, almost
like a corona during a sun eclipse. So

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this is why the corona virus is called
corona virus, because it spikes under the

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electron microscope look like a corona.
And these pictures have no colors, but

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scientists like to colored them in
particular in order to tell people that

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this is a dangerous virus and that is the
background. So if we colored, it may look

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like this. And this is an official picture
released very early in the pandemic by the

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National Institutes as one of the first
pictures of the new corona virus. We can

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also do scanning electron microscopy,
which is a similar measure where you coat

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the entire surface and then you get a
pretty three dimensional picture. What you

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can see here are lung cells, the lung
carpet like the like hairy structure here.

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That's lung cells that are single type two
alveolar epithelial cells. So there are

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like a little like their job is to
get rid of stuff the lungs don't want

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there, like a carpet, they can move and
they get rid of stuff for you. However,

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these cells, you have a problem. They're
infected with corona virus. You can see

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some slime or mucus here, and you can see
the viruses here. Because of the coating,

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they look a little bit like cauliflower.
So that's nice. But it doesn't give us the

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full picture, but so much for people who
say we cannot isolate the virus. We can

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actually even like, make it visible. So we
can make this invisible enemy visible. It

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is just a question of having the right
equipment and a good sample of the virus

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and many hours of work. The virus
therefore exists and can be made visible

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using electron microscopes or, for
example, as a particle accelerator. But

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I'm not going to go into detail here. We
have not enough time tonight. I'm only

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going to talk about electron microscopes
here. So what is the virus made of. Those

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This is the virus. We're going to talk about
this picture later in the talk when we

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talk about model a little bit more. But
here is one Spike, I think you've all

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heard in news from spike proteins, which
cover the surface of the virus or the

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virion. If we draw this schematically, as
Thomas Splettstösser presented for us, he's an

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illustrator, burst in Berlin, it looks
like this. And then we take only the head

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of the spike, which is the region of the
spike we know most about, and then comes

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an animation that I did. So it's not quite
as pretty. If we zoom in, we see the

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surface and below that surface we see
things represented as a ribbon. However,

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we can show this differently. We can show
the individual atoms connected to each

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other. The problem with this display is
that it's really hard to find anything

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here. It is super difficult to get an
overview with this picture, so we prefer

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to show these complicated and fake
molecules made up of atoms as surfaces and

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ribbons. And this ribbon diagram, by the
way, has also been found by a great female

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scientist, Jane Richardson, several
decades ago, which was quite revolutionary

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for my field. So the virus is made up of
atoms and molecules, and they are

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structures can be found out by NMR, X-ray
crystallography and electron microscopy.

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For now, this is all I'm going to tell
you. We're now going to dive very deeply

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into the biology of the virus and what the
structures tell us. And then in the end,

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I'm going to tell you a little bit more
exactly how we actually get from the

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measurement to the model, which holds some
pitfalls and problems for us. And it's an

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area in which I do usually my research.
But first, I'm going to talk about the

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model, you all know this picture from the
CDC, right? And by the way, this thing for

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a scientist, this thing is not a virus,
it's a variant. It's only the transport

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form of the virus, the virus. That's a few
more things that are not contained in this

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little show. That's just a transport form
for its RNA to get into a whole cell. We

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call this a variant. But most people, even
scientists, can also refer to it as the

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virus. So this is the CDC model, right?
That's the picture that went all through

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the press around the world. That's like
THE picture of this pandemic, and it was

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made by the CDC very early on by two
scientific illustrators there. However,

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already then it had some problems. They
made it in quite a rash and it has some

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errors. So we decided to make a new
picture, which looks like this. And. If

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you compare it, two pictures, here are the
differences. The head of the spike in this

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illustration sits directly into the
surface, while in reality it is singing

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sitting on a long, very bendy like rope
like structure that tethers it. So the

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virus, the head of the spike, which binds
to the host cell, is quite flexible. The

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surface is not quite as coarse as shown
here. It's smaller. The virus actually

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relatively large for a virus, and it's got
other proteins swimming in its surface. If

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you look exactly, you'll see the virus is
also not exactly round. Now we thought

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this is not enough. It's nice to have a
picture, but wouldn't it be nice if we

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could actually touch it? So we made a 3D
printable model for those interested. You

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can find also all that information on our
homepage. I'm going to show you the 3D

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model. Let's see. So. This is the virus
model. As you can see, the virus is not

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exactly round because it's outside, it's
very soft. It's like a soap bubble. It can

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change its shape quite drastically. It's
wobbly and the spikes are actually

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stochastic highly distributed. They're not
like regularly arranged and they are

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swimming in the skin. And there are other
proteins in the surface as well, which you

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can perhaps see whether they really formed
as little flower shapes, we don't know.

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And the virus is huge. So this on the same
scale, one to one million as a rhinovirus

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for the common cold. The corona virus is
huge. 20000 base pairs RNA makes it one of

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the largest virus genomes we know. And a
virus, therefore as soft on the outside,

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while rhinovirus has a very hard and rigid
shell that is always composed the same.

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And we need this model in the hopes that,
like other scientists and perhaps schools

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would like to print it at home and
actually like, get something tangible and

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it turned out they did. So we got quite a
few requests from people, from child care

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facilities and from schools and from other
scientists. And even my administration

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like to have them printed. One even
proposed we may have them as Christmas

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ornaments, but I found that a little bit
like tasteless. We didn't do it. And like,

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just before I left Hamburg, we got a new
model. This model is now already a year

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old, and in 2021, signs made quite a lot
of progress. So we now know there are

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fewer spikes and a virus. All in all, it's
a little bit smaller, so it's not quite

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like this, but perhaps less so. It's not
15 centimeters in diameter. The model is

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12, and it is still like potato shaped.
It's not round because now what's

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important for me to show, and I would have
like to show you this model like in front

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of the camera tonight, but. It went into
the museum, it was the first one we had,

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and we brought it to the opening of this
exhibition in Hamburg "Pandemierück in ide

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Gegenwart" the gigawatt, so you can now
see it in the museum and we'll be back in

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my office when they have assembled theres.
And this also holds true. I'm going to

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talk about the task force in the second
half of this talk. But one thing that is

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really true and what's true for this
project as well is the task force is

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typically more interested in new
communication projects than in all the

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pile of stuff we need to finish. You may
notice from home. Right. So this is how

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our model. Now, let's dive deeper into the
thing, because so far we have only talked

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about the virion and only about it's
outside. So the virion has to spike

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proteins on the outside. Two other
proteins M and E protein, it has a double

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membrane hull, which is very thin and
nucleocapsid, which is wrapping the RNA.

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The RNA of actually containing the genes
for everything that the virus needs in

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order to like, take possession of the host
cell. So the RNA is the important bit the

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virion is transporting and nucleocapsid
and everything else kind of packs it and

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makes sure it gets into the host cell. And
I'm going to show you quickly a video

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because I think this is so nice to
understand, and it's the answer to the

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question why does soap help against corona
virus? Because very many, like other

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viruses, are relatively hard to wash off,
but not corona virus, because it's so

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large, it has only a double membrane
shell. And this is a very nice video from

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the protein data bank from our colleagues
there. So this is the virus double

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membrane. It has lipid molecules. You can
see there are hydrophobic on the inside

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and hydrophilic on the outside, so they
lock water on the outside, but not the

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inside. Green molecules are soap. Soap
also has a hydrophobic tail and a

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hydrophilic head. So unlike the water
which stays outside the soap just gets

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into the membrane and kind of like goes in
between the lipids. And then they make

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whole sort of water molecules can get
inside the virus. They can even assemble.

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In around bits of the membrane and get it
out of the virus hull or around a spike

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and remove to spike, which is hydrophobic
to stock out of the virus. This leads to a

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total decomposition of the membrane and
therefore it can be completely dissolved

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by soap. As soon as the nucleocapsid and
an RNA are exposed, the virus is no longer

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infectious. It needs a spike in order to
infect so, you don't need to disinfect

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your hands. You can just wash them with
soap, which I find is so lucky in this

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pandemic because, you know, it would be
really ugly if we would need to disinfect

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everything all the time, but we can
actually just use soapy water. Although,

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let's be honest, I like to use
disinfectant every here, and then it gives

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me just a feeling of more safety. It's
kind of like a ritual to protect me. I

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suspect several of you are the same. So,
so much for the virion, that's like the

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outer shell, that's like the transport
form. But there is more much more. This is

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the corona virus life cycle, or I should
be more correct. It should be called

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infection cycle because technically
speaking, viruses are not life. They need

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a host cell to reproduce. So we're going
to come back to this picture. We're going

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to take this apart bit by bit. First of
all, there is entry entry into oh yeah.

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Let's quickly go back. The thing at the
bottom here, the big thing here. That's

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the host cell. And a little one is
the virus, right? We're clear on that

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Holbrook's here, right? And is the
outside. So this is like your lung

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outside. That's your lung cell inside or
hopefully not your lung cell, right?

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

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

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vector vaccines we see. And I brought you
another model for that, which saw the

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picture here. So this is one to 10 million
scale model of the spike. And this is an

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antibody. Now if you are vaccinated either
by RNA or by a vector vaccine, your body

00:20:36.440 --> 00:20:42.110
overproduce as far as injected with
spikes, which are usually on something to

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.

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

00:20:54.290 --> 00:21:00.290
antibodies that perfectly fit onto that
they can recognize the spike very, very

00:21:00.290 --> 00:21:04.190
exactly. They have a specific binding
site, which is much more rigid than

00:21:04.190 --> 00:21:11.090
anything else the antibody can bind to.
Then this gets decomposed because the

00:21:11.090 --> 00:21:16.260
vaccine is not viable. What remains in
your body is information for these

00:21:16.260 --> 00:21:24.200
antibodies. So now if you get infected
with corona? The immune system antibody

00:21:24.200 --> 00:21:28.710
recognizes the spike it has previously
seen in the vaccine, and that is how the

00:21:28.710 --> 00:21:35.930
vaccine actually works. So having this
protects you, one of the biggest problems

00:21:35.930 --> 00:21:41.140
with COVID 19 infections is that the
immune system responds too late. And then

00:21:41.140 --> 00:21:47.730
too much. So having these makes much more
certain that you will not get severe

00:21:47.730 --> 00:21:55.960
COVID, which is, I think, very nice. And
what we also did, together with the

00:21:55.960 --> 00:22:01.720
animation lab in Utah is not only make
those life life cycle or infection cycle,

00:22:01.720 --> 00:22:06.130
we also made an animation the
scientifically most accurate animation

00:22:06.130 --> 00:22:11.850
available on how the virus actually binds
onto the whole cell. There's a lot we

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

00:22:18.450 --> 00:22:26.320
know the spike protein already. Yes,
nucleocapsid inside there is RNA, which

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

00:22:32.220 --> 00:22:37.820
bottom here is the host cell. So lung
cells actually have ACE2 receptors shown

00:22:37.820 --> 00:22:43.750
in purple, and a spike protein recognizes
those specifically meaning that items like

00:22:43.750 --> 00:22:53.840
a puzzle piece fit exactly onto the purple
receptors on the lung cells. The spikes

00:22:53.840 --> 00:23:01.710
bind there and then something else
happens. Another enzyme also being in the

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

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

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

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

00:23:20.300 --> 00:23:24.870
don't know the mechanism of this. So we
decided to illustrated here with like a

00:23:24.870 --> 00:23:31.480
refolding process and then it's
energetically unstable. So in order to

00:23:31.480 --> 00:23:36.470
become more stable, the whole thing clamps
and folds together, thereby dragging the

00:23:36.470 --> 00:23:41.820
virus and the host cell membrane together,
the two membranes to buy a lipid membranes

00:23:41.820 --> 00:23:49.560
Fuze. The virus material is inserted into
the cell. The RNA is now inside the host

00:23:49.560 --> 00:23:57.050
cell, and this is how infection happens.
So we felt it was particularly important

00:23:57.050 --> 00:24:01.930
to show this to people. We have made this
animation Creative Commons, but

00:24:01.930 --> 00:24:06.160
unfortunately only American television
caught up on it, so we're really hoping

00:24:06.160 --> 00:24:10.250
that one of the German like documentaries
will show this, because we think it's

00:24:10.250 --> 00:24:19.870
really nice to see this process like as
accurately as we can depicted. So here is

00:24:19.870 --> 00:24:24.809
the spike. That's the role of the spike.
Now the nucleocapsid, an RNA a half

00:24:24.809 --> 00:24:32.760
entered into the host cell. What happens
now is that the nucleocapsid dissolves.

00:24:32.760 --> 00:24:38.170
How that exactly happens, we don't know,
but it dissolves and RNA gets immediately

00:24:38.170 --> 00:24:45.030
translated into protein. So the genome
gets RET inside the cell because the cell

00:24:45.030 --> 00:24:49.700
believes it's own either comes from the
host cell and it starts building. The

00:24:49.700 --> 00:24:54.100
proteins encoded in proteins are again
molecules. And actually, it makes one

00:24:54.100 --> 00:25:00.600
very, very long protein chain really long,
which is called the poly protein, which

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

00:25:06.590 --> 00:25:11.610
protein chain into individual molecules
that don't actually can work is called the

00:25:11.610 --> 00:25:16.970
main protease because it's cutting protein
that's called the protease. And these are

00:25:16.970 --> 00:25:22.150
the little triangle shaped things here.
Only when that happens to these bits

00:25:22.150 --> 00:25:26.890
become functional. So if it doesn't
happen, if we can like hindered this like

00:25:26.890 --> 00:25:33.010
cutting off the long polypeptide chain, we
have an efficient drug against corona,

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

00:25:37.880 --> 00:25:44.510
is the drug actually bound two main
protease. So that's what it looks like. We

00:25:44.510 --> 00:25:48.220
are looking specifically for inhibitors,
which will stop this molecule from

00:25:48.220 --> 00:25:52.150
function. So you can imagine this like a
screwdriver that we put out of right point

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.

00:25:57.910 --> 00:26:01.610
And that's like called structure based
drug design. When you actually know the

00:26:01.610 --> 00:26:06.220
structure of the molecule and then you
find a molecule, a small molecule, a drug

00:26:06.220 --> 00:26:13.221
molecule that specifically stops whatever
that protein molecule is doing. It's also

00:26:13.221 --> 00:26:21.230
how many antibiotics work or, for example,
if you've been up long yesterday aspirin.

00:26:21.230 --> 00:26:29.310
Then. From here, where we have the poly
protein thing. Something happens inside

00:26:29.310 --> 00:26:33.830
the cell, the cell is making some kind of
foam, which is connected to the

00:26:33.830 --> 00:26:39.940
endoplasmic reticulum. That's just warm
and inside it. These like enzymes that

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

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

00:26:49.820 --> 00:26:56.640
more RNA. And it does so by a copy
machine, which is called RNA polymerase,

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

00:27:04.950 --> 00:27:13.850
RNA polymerase is an enzyme that makes
more RNA. So one way to block that process

00:27:13.850 --> 00:27:18.990
of making more RNAs, which was similarly,
you know, stop the infection cycle because

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

00:27:24.170 --> 00:27:29.230
remdesivir or so we thought for a long
time. So does this remdesivir. Remdesivir

00:27:29.230 --> 00:27:35.950
looks to the host cell and to RNA
polymerase in particular, like a

00:27:35.950 --> 00:27:41.710
nucleotide, like a building block for RNA.
So basically, things are it's new paper it

00:27:41.710 --> 00:27:47.290
can copy on when in reality it's kind of
explosive like blocks the entire

00:27:47.290 --> 00:27:52.770
polymerase. So you can imagine this like a
Trojan horse, remdesivir is the Trojan

00:27:52.770 --> 00:27:58.809
horse and RNA dependent RNA polymerase is
sure looks like RNA to me and just built

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

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

00:28:10.240 --> 00:28:15.230
our measurements and electron microscopy.
So this is the so-called reconstruction

00:28:15.230 --> 00:28:18.790
density, and that's what we built a
molecule in. So that's like what the

00:28:18.790 --> 00:28:23.450
measurement gave us, everything else we
have to do by hand. So here is the

00:28:23.450 --> 00:28:31.070
density, and this is what the researcher
built into it. The template strand, the

00:28:31.070 --> 00:28:36.870
old one, which is to be copied, is green,
the new one is orange. Remdesivir is

00:28:36.870 --> 00:28:43.080
purple and connected to the end, although
the program doesn't display it as such.

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

00:28:46.880 --> 00:28:54.110
phosphate. So what are more molecules that
researchers modeled in there? Where are

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

00:28:58.130 --> 00:29:01.940
what's happening because it's all very
crowded and difficult to see around it as

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

00:29:07.330 --> 00:29:11.960
other, another building block to the
bottom of the orange chain. It's gotten a

00:29:11.960 --> 00:29:17.149
remdesivir and it tried to put it there
and it successfully did. And this

00:29:17.149 --> 00:29:22.220
structure was taken as to prove that
remdesivir will stop corona. But if you

00:29:22.220 --> 00:29:26.110
look at the density, you can see that the
free magnesium ions and DIPHOSPHATE has no

00:29:26.110 --> 00:29:32.220
density and are not covered by this great
cloud, right? So we think they were never

00:29:32.220 --> 00:29:39.140
really there. And the remdesivir itself is
also not having so much density. So it

00:29:39.140 --> 00:29:43.120
turns out that a structure is not quite
seeing what the researchers did because

00:29:43.120 --> 00:29:48.330
the density doesn't match up with the
structure they built. And as we later

00:29:48.330 --> 00:29:53.090
found out in clinical trials, is that
remdesivir, in fact, doesn't really do

00:29:53.090 --> 00:29:58.280
what people hoped, which, among other
things, has to do with the fact that RNA

00:29:58.280 --> 00:30:03.100
polymerase from corona virus is able to
proofread go like, Oh, there's a

00:30:03.100 --> 00:30:08.980
remdesivir, then go back free nucleotides
take rip out the remdesivir, throw it away

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

00:30:15.120 --> 00:30:18.839
be better, which, by the way, uses a
similar mechanism. It's called a

00:30:18.839 --> 00:30:31.870
nucleotide. Yeah, it's similar to a
nucleotide. Here's another arrow we found

00:30:31.870 --> 00:30:35.070
in the bottom of the structure, only going
to show you because I think the software

00:30:35.070 --> 00:30:40.150
by Tristan Kroll is so cool, it does a
real time molecular dynamics simulation

00:30:40.150 --> 00:30:44.510
while you're dragging around your
structure. We found that there is an error

00:30:44.510 --> 00:30:48.490
in the way the whole molecule was
arranged. If there's any specialist, there

00:30:48.490 --> 00:30:52.100
was a nine amino acid out of reach
associate. OK, I'm going to stop like

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

00:30:56.490 --> 00:31:00.990
you marks up the wrong region and then he
releases it and <i>quickly flying-away noise</i> it goes where it's up to

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

00:31:04.870 --> 00:31:08.309
front of your computer. You need hours to
do this by hand, but his software just

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

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

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

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

00:31:35.419 --> 00:31:40.050
RNA now is exported from the endoplasmic
reticulum. By the time we make this, we

00:31:40.050 --> 00:31:43.750
didn't know how. But Hamburg researchers
and Dutch researchers have now found out

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

00:31:49.370 --> 00:31:53.890
gets packed into new nucleocapsid
were also coded by the genome

00:31:53.890 --> 00:31:59.760
of the virus, then gets wrapped into a new
double membrane, which is host membrane.

00:31:59.760 --> 00:32:05.970
Just it has no spikes, which also were
produced from the genome. And then, of

00:32:05.970 --> 00:32:11.580
course, due the Golgi apparatus is somehow
involved, it gets exported. Of course, for

00:32:11.580 --> 00:32:17.850
everyone that infected a cell, there will
be thousands that are produced and that's

00:32:17.850 --> 00:32:26.120
the entirety of the SarsCoV 2 viral
life cycle. I know, this was a little bit

00:32:26.120 --> 00:32:31.740
much, but I think this is cool and
exciting and just about what, you know. I

00:32:31.740 --> 00:32:36.980
hope the public can understand about this.
It hopefully also tells you why molecular

00:32:36.980 --> 00:32:42.740
structures are important, so they let us
understand how the virus works, how host

00:32:42.740 --> 00:32:48.481
cells are infected. They can help us to
find drug targets and to do structure

00:32:48.481 --> 00:32:53.370
based drug design, where we find drugs
that specifically block these big

00:32:53.370 --> 00:32:59.510
molecular machines from doing their work.
They also help us to understand the

00:32:59.510 --> 00:33:06.549
structures of vaccines and antibodies, and
they also let us understand changes due to

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

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

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

00:33:21.341 --> 00:33:25.340
prediction about what the mutation is
going to change in a functionality. That's

00:33:25.340 --> 00:33:31.850
really important. So in my group, we have
some theories what a Micron actually does.

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

00:33:36.340 --> 00:33:43.240
waiting for research results. But it's
important to understand these molecular

00:33:43.240 --> 00:33:52.169
structures, however, is not very easy to
get them. So what are the problems? When we

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

00:33:58.750 --> 00:34:02.179
spike head that I've shown in the
beginning, right? So the top that you may

00:34:02.179 --> 00:34:06.490
recognize, this looks a little bit like
the blue density here. This is the result

00:34:06.490 --> 00:34:10.919
from our research. And in this case, I
have built almost all of the molecule

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

00:34:15.290 --> 00:34:19.659
tenfold to speed I'm usually using, and I
would usually be sitting there with 3D

00:34:19.659 --> 00:34:24.190
glasses. So here's the density. I said
that with my 3D glasses and this bit

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

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

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

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

00:34:44.240 --> 00:34:49.179
warning from the bin program not reacting
all of the software, it's also not

00:34:49.179 --> 00:34:53.800
commercial. This has been developed by
other scientists, so the usability is like

00:34:53.800 --> 00:34:59.609
so-so cool, just an amazing program. But
if you want some new functionality, you

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

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

00:35:10.549 --> 00:35:13.869
easy, so I try and go, like, now it's
good. Settings should nicely in the

00:35:13.869 --> 00:35:21.890
density and here it's fairly easy. My
students love doing this is like for them.

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,

00:35:25.099 --> 00:35:30.450
get them off the chair, go right up your
physics. They'll do it forever. And

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

00:35:35.289 --> 00:35:45.499
follow, but this is like playing a game.
Away, if you're interested in playing this

00:35:45.499 --> 00:35:54.010
game, we are also having. Like practical
places and stuff. Right! So building,

00:35:54.010 --> 00:35:58.790
building, building, going like, oh,
there's another alanine, I need a pralines

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.

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

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

00:36:12.950 --> 00:36:18.680
this to you in slower again. So you
understand the problem, right? In this

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

00:36:22.720 --> 00:36:28.890
on. I know approximately what a molecule
must look like due to the sequence. So

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

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

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

00:36:41.849 --> 00:36:45.979
measurement data don't tell me enough
about what the model actually should look

00:36:45.979 --> 00:36:55.500
like and several interpretation., everal
models would all be possible. So this is

00:36:55.500 --> 00:36:59.130
kind of difficult. I'm just seeing a
questionnaire that I may want to answer

00:36:59.130 --> 00:37:03.670
right away. Within could is it possible to
verify if you have chosen created the

00:37:03.670 --> 00:37:09.379
right building blocks, you know, the
building blocks because of the genome? So

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

00:37:14.539 --> 00:37:21.839
you started at the right point, the rest
will also be like the correct atoms and

00:37:21.839 --> 00:37:26.039
the correct connection. But how it like
three dimensionally faults, you don't

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

00:37:36.600 --> 00:37:41.910
have to write building blocks at hand.
Usually if there are if there is like, you

00:37:41.910 --> 00:37:46.160
know, if a magnesium ion, for example, is
sitting there, the magnesium ion was not

00:37:46.160 --> 00:37:51.250
in your genomic information. You just need
to know what you're doing to recognize

00:37:51.250 --> 00:37:58.190
this is a magnesium ion ore does this a
diophosphate or something like this?

00:37:58.190 --> 00:38:06.490
Right. Going to answer the rest of the
questions later. Molecular models need to

00:38:06.490 --> 00:38:11.049
be built by hand. This can lead to errors.
There a few automatic algorithms do work

00:38:11.049 --> 00:38:17.059
under favorable circumstances, but most of
the stuff still has to happen by hand. As

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

00:38:21.549 --> 00:38:25.500
new numbers. So we've got 1909 
molecular structures

00:38:25.500 --> 00:38:31.729
today. New structures come out every
Wednesday. There are 1334 from X-ray

00:38:31.729 --> 00:38:36.109
crystallography. That's the thing. With
the particle accelerator in Hamburg, I

00:38:36.109 --> 00:38:41.150
thought, they have been measured at
synchrotrons all over the world. Not only

00:38:41.150 --> 00:38:46.079
Hamburg, where BioNTech structures have
been measured, but also had SARS. There

00:38:46.079 --> 00:38:51.890
have been large screens a diamond in Japan
and China at Sesamia, at Solemy, in

00:38:51.890 --> 00:38:57.349
America. Synchrotrons all over the world
contributed to this. 35 from nuclear

00:38:57.349 --> 00:39:02.470
magnetic resonance, which is a little bit
of a niche method for this type of study.

00:39:02.470 --> 00:39:08.579
And 566 from electron microscopy. 
So 1909 molecular structures

00:39:08.579 --> 00:39:16.339
of different states of 17
macromolecules, 17 proteins from a total

00:39:16.339 --> 00:39:26.789
of 28. So corona virus in total has 28
different genes, 4 proteins. There are 28

00:39:26.789 --> 00:39:33.079
proteins. And we only structurally know 17
of them. And then we have like different

00:39:33.079 --> 00:39:37.119
versions of them, different ph, different
temperatures, spike, head bit of spike

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.

00:39:47.259 --> 00:39:51.980
Errors and structures, as we've
just seen, can happen because fit between

00:39:51.980 --> 00:39:58.940
the data and model is bad, because complete
automation is not possible. Models are

00:39:58.940 --> 00:40:04.819
built manually expertize in many different
areas needed. You need to be good

00:40:04.819 --> 00:40:07.819
software. You need to have done all the
lab work. The measurement needs to be done

00:40:07.819 --> 00:40:12.269
right. Processing needs to be made. You
need to know your statistical validation.

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

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

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

00:40:27.720 --> 00:40:35.789
using and this is where we come in. Small
structural errors can lead to big

00:40:35.789 --> 00:40:41.000
structural problems downstream. Imagine
the bid was to remdesivir, the diphosphate

00:40:41.000 --> 00:40:45.979
there, the fact that there was something
bound into that structure that was not

00:40:45.979 --> 00:40:51.769
really there. But the model had dose like
additional free magnesium ions down the

00:40:51.769 --> 00:40:59.809
line, as I know from insiders, led to like
waste of hundreds thousands of dollars

00:40:59.809 --> 00:41:05.299
and many hours of work time in drug
discovery because they kind of like fed

00:41:05.299 --> 00:41:09.990
this model in order to find a drug that
ultimately never bound because of

00:41:09.990 --> 00:41:17.680
magnesium ion wasn't actually there. So
if we make small structures, that builds

00:41:17.680 --> 00:41:21.599
up hugely for the downstream applications
where they need these molecular

00:41:21.599 --> 00:41:31.279
structures. Errors are common. And now we
add to this an ongoing pandemic. Right.

00:41:31.279 --> 00:41:35.720
And her scientists are there to rescue
today. Lockdown happened, you're sitting

00:41:35.720 --> 00:41:41.339
at home, there are no colleagues to help
you. Your child is home schooling. The dog

00:41:41.339 --> 00:41:45.430
wants to be fed, your grandma calls,
because she's worried and you've got to

00:41:45.430 --> 00:41:50.939
solve the spike structure on which lives
will depend as fast as possible. Normally,

00:41:50.939 --> 00:41:54.450
we take a year to five to solve a
structure, and in the pandemic you only

00:41:54.450 --> 00:42:03.940
got three months. Of course, errors are
going to happen. So that's well, just a

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

00:42:08.779 --> 00:42:14.170
individuals, it's how the whole thing
works. It's such a complex process. Errors

00:42:14.170 --> 00:42:19.539
are going to happen! Now in normal life my
team and I methods developers and

00:42:19.539 --> 00:42:24.589
structural biology. We are the people, who
give us the experimental techniques and

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

00:42:30.670 --> 00:42:36.569
the in the stage like we're usually, you
know. For every Nobel Prize, there have

00:42:36.569 --> 00:42:41.109
been like dozens of Nobel Prizes in
structural biology has been methods

00:42:41.109 --> 00:42:45.059
developed in the background to develop the
methods that made it possible to see, you

00:42:45.059 --> 00:42:49.299
know, the structure of the DNA double
helix or structure of the ribosome, or the

00:42:49.299 --> 00:42:56.029
structure of the influenza virus. It's
just that normally we're just enablers.

00:42:56.029 --> 00:43:05.130
However, here was the pandemic and very
many structures that had errors. So we did

00:43:05.130 --> 00:43:10.509
what we needed to do. We came together as
a relatively large team under my

00:43:10.509 --> 00:43:17.279
leadership, we are today 23 people, we
peaked at 27 last year from nine countries

00:43:17.279 --> 00:43:21.009
to check an improve the molecular
structures of SARS-CoV-1 and SARS-CoV-2.

00:43:21.009 --> 00:43:31.369
So. We are methods developers, most of are
methods developers, we are specialists in

00:43:31.369 --> 00:43:36.441
solving structures. We evaluate all the
published Structures and Protein Data

00:43:36.441 --> 00:43:43.619
Databank or PDB from SARS and SARS-
CoV-2. We reprocess all of them and we

00:43:43.619 --> 00:43:49.549
remodel them, although not all are looked
at manually, because that would be just

00:43:49.549 --> 00:43:53.309
too much. We also do a scientific
dissemination, putting these structures

00:43:53.309 --> 00:43:58.430
into context for people who want to start
doing molecular research on corona virus.

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

00:44:04.680 --> 00:44:10.039
thought the software might be interesting
for you. So every Wednesday come new

00:44:10.039 --> 00:44:14.529
entries of molecules in the protein
databank, which is, by the way, the World

00:44:14.529 --> 00:44:19.039
Wide Protein Databank is an open, open
resource. Everyone in the world can

00:44:19.039 --> 00:44:23.470
download the new structures, and all the
journals require people who make new

00:44:23.470 --> 00:44:28.099
structures to put them there, which is
nice. I'm really privileged to be in a

00:44:28.099 --> 00:44:33.150
field where the data are public. We
compared the new structures with the NCBI

00:44:33.150 --> 00:44:37.950
proteomics, so the genes from corona virus
to find the structures that belong to

00:44:37.950 --> 00:44:44.109
corona virus, put everything into an sql
metha database. Then we calculate how

00:44:44.109 --> 00:44:48.529
different the structures are from the ones
we already know. We look whether all

00:44:48.529 --> 00:44:52.480
measurement data available, so we have a
big problem of not all measurement data

00:44:52.480 --> 00:44:58.640
being published. I hope we are going to be
like astronomy one day, where everything

00:44:58.640 --> 00:45:06.440
gets published. I am sitting in the some
German cometies to that end STIKO AM which

00:45:06.440 --> 00:45:11.059
is a very new hub. And then we run a
number of specialized programs which all

00:45:11.059 --> 00:45:16.349
do validation and put the results on
GitHub immediately. On Thursday, at the

00:45:16.349 --> 00:45:22.160
latest, researchers can find our elevation,
remodeling and the quality indication for

00:45:22.160 --> 00:45:28.770
the structure everything, that can be done
automatically online. We then, for some

00:45:28.770 --> 00:45:33.970
structures, manually rebuilt them, so we
actively look weathered our problems, that

00:45:33.970 --> 00:45:38.200
was, for example, the case with the
remdesivir structure. We tried to do this

00:45:38.200 --> 00:45:42.500
for those structures that we think drug
designers will use the most or that are

00:45:42.500 --> 00:45:47.910
really important. And when we find errors,
we contact our original office first and

00:45:47.910 --> 00:45:55.119
tell them we found an error here is the
corrected structure. Use our data, you

00:45:55.119 --> 00:46:00.929
don't need to cite us, just correct your
structure in the database, please. This

00:46:00.929 --> 00:46:05.269
means we won't get credit, but I meant
that at the beginning of the pandemic,

00:46:05.269 --> 00:46:11.279
people were adjusting their structures
already when the preprint was out, so

00:46:11.279 --> 00:46:15.420
there would not be problems downstream.
And I have often been asked I would like

00:46:15.420 --> 00:46:20.789
to like this again. That was really like
why people accepted our corrections,

00:46:20.789 --> 00:46:25.539
because they didn't need to give anyone
credit. They could just like change them.

00:46:25.539 --> 00:46:30.230
And the database is also online, so
everyone from the Philippines to the U.S.

00:46:30.230 --> 00:46:34.940
can just use them, whether it's like a
commercial person or a taxpayer, or a

00:46:34.940 --> 00:46:40.559
private person research institution, a
foundation, everyone can use our data.

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

00:46:44.309 --> 00:46:51.109
the form of a reference citation. We
disseminate the data via GitHub via

00:46:51.109 --> 00:46:57.190
Twitter. 3D bio notes, which is a three
dimensional database linking directly into

00:46:57.190 --> 00:47:06.640
our database, we contact the offers. We
also have entries in Proteopedia. Molprobity,

00:47:06.640 --> 00:47:11.450
which is a virtual bioinformatics
institute, links directly into our

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

00:47:15.100 --> 00:47:20.440
homepage and we do reviews. There's a lot
of downstream users. The biggest ones are

00:47:20.440 --> 00:47:29.309
the EU Jedi Grand Challenge folding at
home, which peaked out in July last year.

00:47:29.309 --> 00:47:36.809
I think a 2.4 xTFLOPs computing power for
molecular simulations and used in the

00:47:36.809 --> 00:47:43.830
majority our models to start from. And
also very big is IBM open pandemics. But

00:47:43.830 --> 00:47:47.989
there are a number of others, plus many
individual apps. So we found a great new

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

00:47:55.469 --> 00:48:01.489
English version, you can find blog posts
for the public and for scientists. And in

00:48:01.489 --> 00:48:07.020
the end, I would like to talk for like
five minutes about daily life in ritual

00:48:07.020 --> 00:48:14.529
mobility. So my team is over 20 people
from nine to ... we cover nine time zones,

00:48:14.529 --> 00:48:21.520
right? Where nine hours time shift apart.
And we had several lockdowns. So.

00:48:21.520 --> 00:48:26.839
Actually, the majority of people in the
task force, about half of them don't work

00:48:26.839 --> 00:48:31.580
for me. They are volunteering their
researchers elsewhere that volunteer to be

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

00:48:36.349 --> 00:48:43.989
like personally met. So how do you make
group coherence if you are working for 20

00:48:43.989 --> 00:48:49.450
months or 22 months by now in an
environment like this, right? We founded

00:48:49.450 --> 00:48:56.020
ourselves in March 2020 as a chat group
called the Coronavirus Structural Task

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

00:49:02.839 --> 00:49:08.400
plays. We have everyday Zoom meetings at
10 o'clock, one time per week in the

00:49:08.400 --> 00:49:14.700
afternoon. So do people from Oregon can
join us. We do a lot of like media

00:49:14.700 --> 00:49:20.440
outreach in international and German
media. We've been like on nano and Terra X

00:49:20.440 --> 00:49:24.599
and Planet E, we've been in breakfast
television. That was a particularly

00:49:24.599 --> 00:49:30.069
interesting experience. My email got link
to Querdenker and I got a few very

00:49:30.069 --> 00:49:34.579
interesting email exchanges. I also must
say I never got insulted or frightened by

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

00:49:41.589 --> 00:49:49.410
I understood, like how, what the theories
are, and that was very interesting. Keep

00:49:49.410 --> 00:49:53.680
the media also like to write about my
hair, my eyes, blah blah blah on these

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

00:49:58.440 --> 00:50:05.980
years older than me. So really? OK,
whatever. Most importantly, they're

00:50:05.980 --> 00:50:11.300
talking about our research. We also did a
lot of social media. I got a Twitter

00:50:11.300 --> 00:50:15.880
account. Everyone else did as well. You
can watch us work on Twitch if you're

00:50:15.880 --> 00:50:18.930
interested. We found that people find it
soothing to see us modeling these

00:50:18.930 --> 00:50:23.519
structures. I was requested to make
stickers for the team as soon as we got a

00:50:23.519 --> 00:50:28.719
grant and we got funded by the Federal
Ministry for Research and Education in

00:50:28.719 --> 00:50:34.130
2020. We have a YouTube channel where you
can, for example, see the entry animation

00:50:34.130 --> 00:50:40.510
and the students brought a cactus, which
is called Corina the Corona Cactus. I

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

00:50:47.470 --> 00:50:55.119
know, being at home, having to care for
your children. Having people dying. Having

00:50:55.119 --> 00:50:59.880
an ongoing pandemic, knowing that I 'd be
more open pandemics is going to spend

00:50:59.880 --> 00:51:04.589
another million based on your research.
And also that ZDF wants to talk to you and

00:51:04.589 --> 00:51:09.981
the Berliner Abendblatt. This is so
stressful! Think about all the

00:51:09.981 --> 00:51:15.349
responsibility we had, and it was really
terrible for us, so we needed to cheer up

00:51:15.349 --> 00:51:19.999
every here and then, the whole group kind
of like grew together and we all became

00:51:19.999 --> 00:51:25.999
friends. This was unheard. For us, it was
very uncommon as researchers. Typically,

00:51:25.999 --> 00:51:29.029
our behavior with each other is much more
formal than their behavior and this group

00:51:29.029 --> 00:51:35.880
was. But these were like exceptional
times, and we wanted to fight the pandemic

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

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

00:51:49.340 --> 00:51:53.289
talking to right audience, right? We have
a group chat. Do you know what that looks

00:51:53.289 --> 00:51:57.759
like? Let me tell you. Typically,
professors don't communicate with this.

00:51:57.759 --> 00:52:05.869
We have a virtual, Oh, we have a
virtual space. We hope to change to work

00:52:05.869 --> 00:52:13.130
adventure soon. We all want to play games
in the evening occasionally with the

00:52:13.130 --> 00:52:17.960
group, so we do some team building
efforts. When people can meet in person,

00:52:17.960 --> 00:52:22.540
they usually do and sometimes they go and
travel and like, meet each other. But this

00:52:22.540 --> 00:52:31.079
has been very limited. And we did grow
together as a network, that will be there

00:52:31.079 --> 00:52:37.390
after the pandemic, so we are 25 people
all over the planet that did this

00:52:37.390 --> 00:52:43.980
together. And even if we wouldn't have
made any difference against the virus, I

00:52:43.980 --> 00:52:49.890
would still be happy to have done it for
the friendships I made. However, we did

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

00:52:54.910 --> 00:53:00.509
and the results could be gotten by
everyone without reference. But we know a

00:53:00.509 --> 00:53:07.700
few things wouldn't have happened without
us. And I'm. Deeply grateful for having

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

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.

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

00:53:35.630 --> 00:53:43.619
year contracts already out of all my task
force members, there is only one holding a

00:53:43.619 --> 00:53:50.849
permanent position and two which are
retired. Everyone else, including six

00:53:50.849 --> 00:53:56.990
people whose contract is going to run out
next year, are on temporary contracts and

00:53:56.990 --> 00:54:02.140
not students. Students are extra. That the
students are on time limited contracts is

00:54:02.140 --> 00:54:08.380
OK, but Germany's got a problem. 84
percent of academics in German

00:54:08.380 --> 00:54:17.529
universities are on time limited
contracts. So are we. Only one task force

00:54:17.529 --> 00:54:22.779
member has was a permanent position
signed, and that's not me. And this is not

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

00:54:27.440 --> 00:54:32.380
exposure I had, but there are people out
there who are single moms and dads, who

00:54:32.380 --> 00:54:36.769
come from less privileged backgrounds or
had a harder life and who can just not

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

00:54:44.740 --> 00:54:48.920
all these bright people and I'm seeing
them right. They leave my institute and

00:54:48.920 --> 00:54:52.759
they go to industry. And then the
universities complain that they're not

00:54:52.759 --> 00:55:00.700
competitive. We need to change the system.
We need to have more permanent positions

00:55:00.700 --> 00:55:07.309
in science. I promise we won't perform
worse, if you give us permanent contracts.

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

00:55:16.989 --> 00:55:22.029
virus and its life cycle, we need to
understand its molecular biology. This

00:55:22.029 --> 00:55:27.759
will help with the design of therapeutics.
We evaluated these molecular structures

00:55:27.759 --> 00:55:32.869
with a bespoke pipeline, an expert
knowledge provided context and reached out

00:55:32.869 --> 00:55:37.969
to the taxpayer and the general public to
inform them. We also wrote a paper

00:55:37.969 --> 00:55:43.400
together with long off a list making the
invisible enemy visible, which is our

00:55:43.400 --> 00:55:49.129
motto. And as we started this all with
questions, I'm going to end with

00:55:49.129 --> 00:55:55.239
questions. Structural biology remains
difficult. What can we learn from our

00:55:55.239 --> 00:56:01.499
findings? Should we, as a scientists
community, change our attitudes towards

00:56:01.499 --> 00:56:10.640
errors? Should this serve as a model for
other projects, cannot serve as a model

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

00:56:14.400 --> 00:56:18.809
was writing a comment whether we believe
that science should always be like this?

00:56:18.809 --> 00:56:23.459
My God, that would be awesome. I would
totally be up for it if science would

00:56:23.459 --> 00:56:27.009
always be like this! Come together with a
bunch of friends, but without funding!

00:56:27.009 --> 00:56:32.210
Start doing something to, you know, fight
a global pandemic, then get some funding.

00:56:32.210 --> 00:56:39.489
Still, having like no senior people on a
project. Can open science compete? I don't

00:56:39.489 --> 00:56:49.099
know. We get pretty little credit. It
would, definitely. OK, science compete. I

00:56:49.099 --> 00:56:53.289
don't know, it doesn't quite look like it
still getting measured only by the

00:56:53.289 --> 00:56:58.979
citations my paper gets. And well, at
least a paper is not behind a paywall, but

00:56:58.979 --> 00:57:02.799
if we would have published all our stuff
in like papers would possibly get more

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

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.

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.

00:57:22.200 --> 00:57:26.859
He's writing our first Alpha article about
a corona virus protein. I feel that the

00:57:26.859 --> 00:57:31.259
German academic system and all over the
world, actually you need to be older and

00:57:31.259 --> 00:57:37.119
older to become a professor and be
permanent and be like a grant holder. I

00:57:37.119 --> 00:57:41.180
don't think it's necessary, I think that
professors could be 30 and the world

00:57:41.180 --> 00:57:49.030
wouldn't, you know, like, go down. Well,
what will change in science after a

00:57:49.030 --> 00:57:54.289
pandemic? We had like large exposure. It
certainly will also have to do with like

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

00:57:58.580 --> 00:58:03.720
change how people view science, I'm sure.
How will scientists be viewed by the

00:58:03.720 --> 00:58:08.960
public? Right. Right now, of course, you
know, mom and dad are very proud, but.

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

00:58:14.119 --> 00:58:19.180
are. But I'm like general, exclusively
taxpayer funded. I never took any money

00:58:19.180 --> 00:58:23.519
from the pharmaceutical industry. I have
like, you know, no stakes in this game.

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

00:58:31.959 --> 00:58:35.420
difficult things there, how people regard
science, but definitely the pandemic is

00:58:35.420 --> 00:58:40.079
going to change, how science is going to
be viewed. What's that going to be?

00:58:40.079 --> 00:58:48.400
<i>Exspiration</i> In the end. I'd like to
thank all the task force members and all

00:58:48.400 --> 00:58:54.000
our collaboration partners and our
scientific fairy godmother, Alvin Pearson,

00:58:54.000 --> 00:58:59.099
who had little role in this research but
much role in our mentorship and bringing

00:58:59.099 --> 00:59:04.299
us forward. My home, the University of
Hamburg, the Coronavirus Structural

00:59:04.299 --> 00:59:08.499
Taskforce, our we are funded by the
Deutsches Officials Command Trust and the

00:59:08.499 --> 00:59:13.699
Federal Ministry for Research and
Education. I would like to point out that

00:59:13.699 --> 00:59:19.130
we are looking for student assistance, not
only for scientific work, but also for

00:59:19.130 --> 00:59:25.430
social media video and programing work and
3D printing. So if you know anyone who's

00:59:25.430 --> 00:59:30.710
interested, please point him in my
direction. My email is there. We are also

00:59:30.710 --> 00:59:36.219
offering Bachelor, Master and Ph.D. thesis
in areas that cover both Lab work and

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

00:59:43.691 --> 00:59:50.990
internet and on Twitter and. I'm looking
forward to the discussion. And thanks for

00:59:50.990 --> 00:59:53.549
listening.
melzai_a: You write it, so.<i>laughing</i>

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

00:59:57.660 --> 01:00:01.519
on dislike committees more and more, I'm
reaching an age where I'm sitting on

01:00:01.519 --> 01:00:05.359
committees and I told them legacy software
is a problem.

01:00:05.359 --> 01:00:07.900
melzai_a: It's a real.big problem.
Andrea: You know, it's very troubling that

01:00:07.900 --> 01:00:12.829
the software is written in Fortran. Not
every second Linus go to, so it's written

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

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

01:00:21.530 --> 01:00:24.810
lost.
melzai_a: Exactly. And they are. So you

01:00:24.810 --> 01:00:28.459
have to first influence to grant writing
institutes that there are grants out so

01:00:28.459 --> 01:00:32.849
that this software can read is reversed.
And this software is not easy. So that's

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

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,

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

01:00:45.629 --> 01:00:49.990
to eat. <i>laughing</i> It was very
interesting. So I can also this and you

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,

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

01:01:00.739 --> 01:01:05.900
just my sense of that one.
Andrea: So I brought my Ph.D. thesis. I

01:01:05.900 --> 01:01:08.329
worked on chalex?? and that faces similar
problems.

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

01:01:15.319 --> 01:01:20.359
structure. There is more or less it was
like, Yeah, so questions were the

01:01:20.359 --> 01:01:25.440
questions. Frankly, we ain't got a first
question, I think around 20 or 30 minutes

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

01:01:30.269 --> 01:01:34.969
picking up all of these points. And so the
first question was how do the virus

01:01:34.969 --> 01:01:37.400
variants affect the shape or form of the
virus?

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

01:01:44.329 --> 01:01:48.690
there should be fewer spikes and should be
a bit smaller. But nothing would change on

01:01:48.690 --> 01:01:54.920
this view, like the scale is way too
large. The mutations each change about 10

01:01:54.920 --> 01:02:01.099
atoms, so every like amino acid at this
different, it's about 10 atoms. And those

01:02:01.099 --> 01:02:06.420
changes would be so small you could not
see them on the virus model. You'd

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

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

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

01:02:20.499 --> 01:02:28.079
binds to the host, to the host cell, to
ACE2 receptor, and that binding is highly

01:02:28.079 --> 01:02:35.920
influenced by this by the mutations. Now
we found that we may end up lucky because

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

01:02:41.729 --> 01:02:47.380
cell. So everything that would mate
despite change in a way that the antibody

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

01:02:55.170 --> 01:03:03.000
the host cell. However, it seems that
Omicron is still able to bind human cells

01:03:03.000 --> 01:03:08.780
very efficiently, while antibodies cannot
recognize it so easily. That may have to

01:03:08.780 --> 01:03:13.099
do with like this finger's actually like
packed and you could imagine like putting

01:03:13.099 --> 01:03:17.999
cotton wool around it. That's called
glycosylation. It's got long sugar changes

01:03:17.999 --> 01:03:22.840
that are rule, and they're there to
obscure the immune system, like the

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

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

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.

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

01:03:44.529 --> 01:03:50.819
tiny changes. And another change that
happens in Omicron as well is the

01:03:50.819 --> 01:03:56.799
proofreading mechanism. When the RNA is
copied is like damaged and we think it's

01:03:56.799 --> 01:04:01.869
damaged. So their so-called eNd RNA, which
is a proofreading protein, its sharp is

01:04:01.869 --> 01:04:06.630
like to go like a star and correct? Yes,
correct, correct. Correct. That seems to

01:04:06.630 --> 01:04:10.959
be a little bit broken. So it could be
that Omicron is accumulating so many

01:04:10.959 --> 01:04:17.229
mutations because it's RNA copy machine.
It's like not working as it should is

01:04:17.229 --> 01:04:21.630
basically not proofreading. That would
mean that more viruses are produced that

01:04:21.630 --> 01:04:26.549
are not viable and cannot survive. But it
would also mean that it mutates much

01:04:26.549 --> 01:04:32.009
faster, and we think that may have an
influence. But that's just theory. So far

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

01:04:36.799 --> 01:04:42.059
yet, because it's just a theory, but it
would make sense, right?

01:04:42.059 --> 01:04:46.400
melzai_a: Connected to that, I would have
a question the ice receptor of small children

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

01:04:51.339 --> 01:04:56.049
because all the concern to what's more,
the smaller children are the defense.

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

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

01:05:06.249 --> 01:05:08.319
say anything about it than say something
that's wrong especially.

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

01:05:11.839 --> 01:05:19.099
that everybody can look at them and.
Andrea: Know we live in an age of

01:05:19.099 --> 01:05:23.079
preprint, and very often the PDB papers
are there when a preprint comes out, which

01:05:23.079 --> 01:05:28.079
is how we called so many errors, right?
They published a preprint, they put out a

01:05:28.079 --> 01:05:32.349
structure. We went like, there's errors in
the structures. And then when they

01:05:32.349 --> 01:05:34.880
published actual paper, everything was
corrected.

01:05:34.880 --> 01:05:39.380
melzai_a: And she's agreed that believe
the changes, I think are checked on the

01:05:39.380 --> 01:05:42.619
PDB.
melzai_a: This is, in fact, because yes,

01:05:42.619 --> 01:05:45.799
that's that's what IT people like
because then that, you know, there's a

01:05:45.799 --> 01:05:52.079
history is very important. And there's a
second question and it goes towards the

01:05:52.079 --> 01:05:54.119
tools that I use to simulate those
molecules.

01:05:54.119 --> 01:05:59.359
Andrea: Wait, wait, wait, wait. I have a
follow up to this: thing that I would

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

01:06:03.890 --> 01:06:09.229
where only original offers are allowed to
change their structures. Now, imagine if

01:06:09.229 --> 01:06:14.859
the protein data bank would be like GitHub
with pull requests. We could go like, go

01:06:14.859 --> 01:06:18.789
like, changed the molecule around. Go
like, no, it's a better fit to your data.

01:06:18.789 --> 01:06:22.979
Please pull.
Herald: That would be a very subversive

01:06:22.979 --> 01:06:26.259
proposition. I would say.
Andrea: Yeah, wouldn't that be nice? I'm

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

01:06:31.319 --> 01:06:35.769
that we have like repositories for a while
in software development. We could do the

01:06:35.769 --> 01:06:44.049
same thing with models fitted to our
experimental data. But I think I need to

01:06:44.049 --> 01:06:47.999
go into more committees.
melzai_a: Yeah, it sounds like this. I

01:06:47.999 --> 01:06:53.839
would agree for that proposal. There was a
person that was asking about the toolsset

01:06:53.839 --> 01:06:58.539
that you would use to simulate those
molecules and structures and so on. And if

01:06:58.539 --> 01:07:03.599
you then create these more usable pictures
for the public, how do you balance

01:07:03.599 --> 01:07:08.449
artist's impression simplified models and while keeping the scientific truth as

01:07:08.449 --> 01:07:14.160
much as well as possible.
Andrea: The question you don't need the

01:07:14.160 --> 01:07:17.719
public even to have this problem. You have
it already when you make pictures

01:07:17.719 --> 01:07:21.589
scientifically. Because sometimes you want
to show our certain aspects of a molecule

01:07:21.589 --> 01:07:26.630
very clearly, which means you have to cut
away, for example, a part of the molecule.

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

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

01:07:35.329 --> 01:07:38.809
with one program and then you take all the
coordinates of the atoms and you throw

01:07:38.809 --> 01:07:44.569
them into a professional rendering program
that like, we'll do it all pretty. But you

01:07:44.569 --> 01:07:48.930
still have to make an executive decision
on what to show in your graphics, in your

01:07:48.930 --> 01:07:56.799
paper. And I think that in particular,
structural biologists, who deal with three

01:07:56.799 --> 01:08:01.329
dimensional and two-dimensional pictures,
we would do very well to think a lot more

01:08:01.329 --> 01:08:07.769
about scientific illustration. So all my
team likes thinking about these things,

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

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

01:08:17.890 --> 01:08:21.980
going to stick. But it turns out that
scientists also need these tools to

01:08:21.980 --> 01:08:26.830
understand what's going on. It's like
actually having a 3D model helps you so

01:08:26.830 --> 01:08:32.420
much with thinking about things. Crick and
Watson. They build a model of their DNA in

01:08:32.420 --> 01:08:37.160
metal for a reason. Because we're looking
at three dimensional things, making them

01:08:37.160 --> 01:08:43.560
like understandable with our hands. So
yes, as a good researcher, you're not only

01:08:43.560 --> 01:08:48.739
able to explain your research to the
cleaning woman, you should also be able to

01:08:48.739 --> 01:08:53.290
visualize it properly. And it's part of
the art. If you are a structural biologist

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

01:08:58.310 --> 01:09:02.239
structural biologist. End of story. You're
in the wrong discipline, you should have

01:09:02.239 --> 01:09:05.359
possibly chosen something where you need
less graphics.

01:09:05.359 --> 01:09:12.069
melzai_a: And I think one of your industry
does is actually a of biologist by

01:09:12.069 --> 01:09:17.699
training. Right? I think you've got...
Andrea: Tomasello is a proper biologist.

01:09:17.699 --> 01:09:25.589
Thomas Splettstössersplit shrews as a prop about like a
Ph.D. in bioinformatics and Janet Erosa,

01:09:25.589 --> 01:09:32.569
and LiU are both scientists who are having
a group that only deals with illustration.

01:09:32.569 --> 01:09:36.460
So it's actually in science. We have
several groups in the world and structural

01:09:36.460 --> 01:09:41.690
biology who only do illustration as
science. So David Goodsell with his

01:09:41.690 --> 01:09:48.179
watercolors, is very well known, but Janet
Erosa is another one. So actually making

01:09:48.179 --> 01:09:54.880
these animations and pictures is so
complicated that television can't do it.

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

01:10:00.480 --> 01:10:06.090
Rizzo and Nano with us. But then they
asked my expertize to make another

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

01:10:11.429 --> 01:10:18.630
published a completely wrong animation of
the entire viral mechanism under my name.

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

01:10:24.690 --> 01:10:29.469
wrong structure of the virus for which
they claim that I helped them make it, and

01:10:29.469 --> 01:10:34.530
I wrote to them and told them, Your
depiction of the virus is wrong. I can

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

01:10:43.199 --> 01:10:49.830
care on. I guess they think it's not
important enough, but I think with a

01:10:49.830 --> 01:10:55.050
threat like this where we really cannot
see the virus, it is important to bring to

01:10:55.050 --> 01:11:00.679
the public the best possible depiction we
can deliver. Sometimes, however, as I

01:11:00.679 --> 01:11:05.010
said, you omit certain aspects, for
example, to show the effects of a mutation

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

01:11:12.619 --> 01:11:15.830
really an important part of what we are
doing. Like pointing out the important

01:11:15.830 --> 01:11:18.130
bits of ...
melzai_a: Scientific information is so

01:11:18.130 --> 01:11:23.900
important, I think we have one final
question, which I would say comes out

01:11:23.900 --> 01:11:30.460
comes towards the direction of the immune
system. And the question would be can you

01:11:30.460 --> 01:11:35.949
can you define vaccine on purpose so that
the immune system can forget how to

01:11:35.949 --> 01:11:39.889
produce the antibodies after a defined
period of time? And I think the concern

01:11:39.889 --> 01:11:48.670
here is about increasing your 
financial gain in the crisis, for example.

01:11:48.670 --> 01:11:55.540
So programed obsolescence, as both of
those mentioned. So you're a bit late. So

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,

01:12:00.800 --> 01:12:08.480
that's not possible. You can make. You can
enhance how long vaccines and how much

01:12:08.480 --> 01:12:13.929
immune response you get from a vaccine or
certain additives. But you can not, like

01:12:13.929 --> 01:12:18.810
make them a definite time because
everybody is different. So even when you

01:12:18.810 --> 01:12:21.840
get your booster shot, they say six
months, but you may need it after three

01:12:21.840 --> 01:12:27.550
months or you may need it after 12
authorityto. It's very hard to tell. And

01:12:27.550 --> 01:12:32.520
pharma industry does not have tools that
would allow them that, to my knowledge. So

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

01:12:38.690 --> 01:12:43.780
system, and so complex is the rocket to
the Moon. So.

01:12:43.780 --> 01:12:46.860
Andrea: I think it's a it's a valid
concern. It's just technologically not

01:12:46.860 --> 01:12:53.429
possible. Luckily, I guess. 
melzai_a: The final and really last question, I think,

01:12:53.429 --> 01:12:57.110
is where can somebody find the 3D models
out there?

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

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.

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

01:13:21.110 --> 01:13:29.380
thingy worse. It's also called inside
corona. And you can also write me a

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

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

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,

01:13:49.840 --> 01:13:53.260
not in December 2008. Yeah, exactly. Or
printed?

01:13:53.260 --> 01:13:59.960
Andrea: Yes. So thank you very much for
having me.

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.

01:14:02.820 --> 01:14:08.280
Everybody. All right. Oh, you know how it
looks like? I think that's really

01:14:08.280 --> 01:14:12.020
important. I think one and a half years
ago, I came across the first pictures was

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

01:14:17.710 --> 01:14:26.090
the scientific original papers because
they are so difficult to read. So. Yeah.

01:14:26.090 --> 01:14:34.130
Good. You know. And thanks for being here
and looking forward to hearing and seeing

01:14:34.130 --> 01:14:38.050
more and hopefully once this will be over.
I think

01:14:38.050 --> 01:14:43.730
Andrea: I hope so too. Going back out of
the spotlight to being just a Methods

01:14:43.730 --> 01:14:45.730
developer, that would be nice. 
Herald: That would be nice, yes.

01:14:45.730 --> 01:15:05.000
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