WEBVTT - generated by Videoportal Universität Freiburg

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Welcome. I am pleased to introduce the Centre
for Integrative

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Biological Signalling Studies at the University
of Freiburg to you today.

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Here you see twice 30 trillion

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cells, on on hand these cells form 43 cubes
of baker's yeast and on the other hand these
cells

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30 trillion cells form a healthy human organism.

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Why can these human cells form such a large,
healthy organism

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whereas these yeast cells can only form 43
cubes of baker's yeast?

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A very important reason is, that human cells
or cells from

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multicellular organisms can talk to each other
in order to

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Work together, so that each cell knows what
it has to do in order to

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To get the whole organism to develop and be
healthy

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This cellular communication takes place everywhere
in biology.

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Between individuals, in animals, in plants,
but also

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within single cells there are many communication
processes.

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We in CIBSS want to understand this universal
language, this universal

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communication of life and we want to learn
to speak it too.

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The challenges we have set ourselves are great,

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because such biological communication processes

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take place on many different scales from the
size of a molecule of

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0.5 nanometres up to the size of an entire
organ.

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That would be like, if we would make a reaction
now

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we would have an element which is about the
size of a

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one cent coin and it would be able to influence
the appearance of the moon.

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Similarly, these communication processes occur
on very different time scales.

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Individual signal processes last 100 microseconds
and these processes that

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last 100 microseconds, can end up influencing
the life cycle of an

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organism in the range of a year, for example,

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It is as if we were dealing with a process
which lasts one second,

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and could change the whole time span from the
Ice Age until today.

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To illustrate how these signalling processes
take place in our bodies

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I would like to show you an  example, the corona
vaccination.

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When you get vaccinated, the

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vaccines of this messenger RNA are injected
into the muscle.

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There it takes 30 minutes until this messenger
RNA is absorbed into the cell.

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Within two hours this messenger RNA

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is translated into viral proteins, which are
then detected within another two

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hours by dendritic cells of the immune system

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These dendritic cells act as transporters and
bring

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these proteins to the lymph nodes  within three
hours

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In the lymph nodes it then takes about one
hour for T-cells -

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these are other cells of the immune system
-

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To recognise these viral proteins as something
that does not belong in our body.

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This recognition takes place within

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half a second and after five seconds the entire

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T cell knows that there are proteins here that
don't belong in the body,

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and thereupon the T-cell multiplies.

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and builds up an immune response against these
viral proteins.

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The building up of this immune response takes

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several days and can then give protection that
lasts for months or years.

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In CIBSS we would like to investigate such
and many other signals in living organisms,

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similar to what we humans receive every day,
a wide variety of signals;

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Through computers, newspapers, letters, radio
and so on, there are also many kinds of

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biological signals that we listen to, that
we want to understand,

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There are signals at the level of molecules.
at the level of cells. at the level of

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organelles or whole organs.

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and to understand these signals and

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so that you don't just hear a loud ramble,
it is important that

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you are able to examine individual signals
in isolation.

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Like when you now concentrate  on the speaker
even though

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there are a lot of background noises.

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To study these biological signals so precisely
we need specialised

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devices. For example, devices with which we
can recognise structures.

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They can detect 10th billionths of a metre.

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The smaller the thing is that you are wanting
to examine

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the larger, the bigger the equipment has to
be.

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For example, a cryo electron microscope.

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with which we can explore what individual molecules
look like.

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These cryo electron microscopes are very

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expensive. they cost 6 million euros, are about
three metres high

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and are super sensitive to disturbances.

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For example, they cannot be used in a

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street where a tram is passing, because the

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vibrations alone would disturb the signal in
the microscope.

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Another example of how we can use such

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communication processes you can see here.

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We develop special techniques for this

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techniques with which we can make the signals
visible.

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Here you can see the brain of a zebrafish

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in which four different signals can be viewed
at the same time.

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And we got this brain to light up

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in a colour whenever a certain signal is active.

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Now, if we can view a brain like this over
time

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In the zebra fish, we can see exactly,

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when which signal in which cell  is important
in order to subsequently

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get an entire functional zebra fish brain.

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If we now understand such individual signals

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here, with cryo electron microscopy or here
with these

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colouring signals, another great challenge
follows.

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We have to cross-reference the signals with
each other, because all these

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different signals that we measure in the body
and in an organism

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only make sense when we cross-reference these
signals with each other.

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If we integrate the signals with each other.

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Now I would like to give you some

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examples from current research in CIBSS.

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Where are we learning to understand the language
of life?

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Through our basic research in CIBSS we generate
new knowledge, which is then

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subsequently translated into medical innovations.

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For example, researchers have

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found that corona viruses when they go into
cells, they cause

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the cells on the surface to form such thin
protrusions on the surface.

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And it has been shown that the Corona Viruses

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then sit in the tops of these protrusions.

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And this was recognized as a new mechanism
for

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the spread of viruses from one cell to the
next cell.

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And if it is now known how the virus affects
the cell, it is

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a possibility to develop drugs specifically
against it.

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Another research topic in CIBSS is

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the investigation which active substances,
which potential

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drugs are able to activate immune cells so-called
macrophages,

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so that they are more efficient against cancer
cells for example, and the search for

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such new agents that activate immune cells
against cancer

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have a high potential to be used in cancer
therapy.

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We are looking at this,

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because when we are able to understand the
individual signals

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how, for example, a cancer cell communicates
with an immune cell,

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it is the first step towards being able to
influence the signals,

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For example, for better therapy possibilities.

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Here I would like to show you how we can not
only

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understand biological language, but how we
try to

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actively communicate to create new innovations.

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Here you see, for example, a clover plant.

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A clover plant that grows really well here,
and here a somewhat stunted clover plant.

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Why can this clover plant grow so well?

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The reason is that this clover plant has begun

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communicating with bacteria that live in the
soil.

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And this communication has led to the fact
that the bacteria now live in so-called

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rhizobiaceae in the roots of this plant.

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What are the bacteria doing there?

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These bacteria convert nitrogen which is abundant
in the air

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into nitrogen fertiliser, which the plant needs
to grow.

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Therefore plants grow, such clover plants or
other

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crops like beans or soya still grow pretty
good on nitrogen-poor soil,

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if they have these rhizobiaceae.

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If they don't have these rhizobiaceae,

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they can't grow properly whithout the fertiliser.

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And in CIBSS we are now trying to teach.

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this ability of communication between roots
and bacteria to other

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crops such as cereal crops.

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so that  the heavy use of nitrogen fertiliser,
artificial

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nitrogen fertiliser in agriculture can be dispensed
with.

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This not only has great potential for sustainable
agriculture in the

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developed countries, but also a very big potential
in developing countries.

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where there is simply no money for expensive
artificial nitrogen fertiliser.

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If we now want to actively communicate with
such biological signals like this,

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if we want to talk to the plant or an organism
or a cell,

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We want to make contact. we must also speak
a language that

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the organism, that the cell can understand.
How can we do that?

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An example on which we in CIBSS are very

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actively researching is the so-called optogenetics.

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Optogenetics aims to make it possible for us
to give

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light signals to cells, to organisms, on organisms,
on organs, and with these

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light signals tell the cells what the cells
should do.

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How can we do that?

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Because a normal human cell,

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muscle cell or liver cell does not react to
light,

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Synthetic biology helps here.

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For this we have looked at other organisms

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that can react very well to light.

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These are plants.

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How do plants perceive light?

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Plants have specific components, proteins that
react to light.

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This means that if a plant, for example, senses
red or blue light,

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these photoreceptors change their shape or
interact with each other.

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Which then finally triggers the response of
the plant to the light.

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What have we done to use this?

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We have taken the genetic information

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of the plant, which contains the information
for these photoreceptors, and converted it
into

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another cell, for example a human cell or mammalian
cell,

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This information is read in the mammalian cell.

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This is how these photoreceptor

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proteins are produced and if we now shine red
light onto one of these

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mammalian cells, it causes these two,

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photoreceptors, for example to interact with
each other,

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This means that with optogenetics one can use
light as a switch, as a communication signal

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And through this interaction of two proteins,
we can now regulate biological

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signals in such mammalian cells for example,
activate individual genes

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or stimulate the cells to divide or to differentiate.

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This means that with optogenetics one can use
light as a switch, as a communication signal

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to interact with biological systems

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for future applications in gene therapy.

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Gene therapy is aimed at introducing

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correct genetic material into the genetic material
in humans

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in order, for example, to fight hereditary
diseases.

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What is the procedure for gene therapy?

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The therapeutic gene is inserted into a viral
vector, a so-called gene vector

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for example a so-called AAV vector

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And these AAV vectors are able to then dock
on human cells

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and insert their therapeutic gene into the
cells to correct a defective gene.

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for example in a hereditary disease. Now the
problem is,

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that these AAV vectors can go into a lot of
different calls

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maybe even into cells where we don't want them
to be. where we don't want them to go.

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And this is where optogenetics can help.

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To do this. we have developed a system that
allows this gene shuttle to enter only

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into the cells that we illuminate with red
light.

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How did we go about it?

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We first blinded this virus so

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that it can no longer recognise the cells.

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And then we put a mediator protein onto the
cells.

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And this mediator protein has the

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property that when we illuminate it with red
light, that it then changes its shape

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so that it can be perceived again by this gene
vector.

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This gene vector then docks to the cell,

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enters the cell and adds the therapeutic gene,

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the therapeutic genetic material. so that then
the genetic defect is corrected in the

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cell where we want it to be corrected, whereas
all the other cells

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cannot take up this viral vector, this gene
shuttle.

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These lines of research that I have just presented
to you, are only a few

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examples of the many research projects that
are going on in CIBSS.

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You have seen that we are researching signals
from small to large, from short to long

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and that we would like to communicate using
these signals.

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This can never be done by one person alone

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and that is why CIBSS has a total of 69 working
groups on this project,

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How do we finance such a big research?

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We were successfull in a long hard

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competition of the so-called Excellence Strategy
in Germany

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and raised 37 million euros to then within
seven years be able to

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research these challenging topics.

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If you would like to learn more about biological
signalling research,

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we cordially invite you to get in touch with
us.

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We offer regular training for

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pupils and students, as well as for teachers.

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And we develop school experiments that participants
from such training courses

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can take back to school and conduct for themselves,
real experiments

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on biological signalling research.