- So, thanks, Meredith. So if everybody wants
to leave the audience, it's time to do it, because
she did my talk much better than what I could do. [LAUGHTER] So, yes, thank you very
much for being wonderful. And thank you to all
of Radcliffe's staff for doing a fantastic job. I don't name all
of them, because I would forget some names. This year, this
fellowship, is incredible. You have made it
fantastic for me, really. And thank you to
Emma [INAUDIBLE] and Alyssa for being here. And thank you to
my fellow fellow for being such a warm and
outstanding and challenging crowd. I've learned so many
things, and I will miss you. So in the next 45
minutes or so, I'll try to use my most
poetic language, which is not very good, to try
to explain to you what we do in my lab in Paris and
what I've been doing here at Radcliffe. So I'm a cell biologist. And as Meredith said, I work
in the Institut Pasteur, which you can see here. This is the building
which was the home and laboratory of Louis Pasteur
in the last years of his life. And on the other
side of the road, this is another
beautiful building, and this is my lab,
[SPEAKING FRENCH].. Not bad at all. It's very inspirational
to have the Pasteur home in front of me. So in my lab, in Pasteur, we
try to understand how cells work and what goes wrong in disease. A cell, from the Latin
"cella," means a small room. And cells are the
basic structural units of all known living organisms. Each cell is able to function,
replicate, divide, and work by itself and is also
able to differentiate in many different types of
cells that come together and form different tissues
and different organs, which perform all the
functions in our body. Now, let's look at the cell. A cell is surrounded
by a membrane, which is called plasma membrane. Cells are not really round. They can have different shapes. And each cell is able to
extend different little hairs or extensions, which
could be called cilia, or little arms, that
are used by the cell to sense the surrounding. Inside the plasma membrane,
there is the cytoplasm. That is like a thick
minestrone soup. So they have all the
little organelles here. It's full of little organelles
that are little organs, because they perform all
the functions of the cell. In the middle, you
have the nucleus, which is the central
direction operation. It contains the DNA,
the genetic material. And here you have
the mitochondria. These are the power stations. They make the energy
for the cell to work. And here you have the
lisosomes, also very important. They are the cleaners. They would clean up the garbage
and recycle the goodies, and they're very
good at doing that. And here, this
reticular structure in called endoplasmic reticulum. Here, this is the factory
where all proteins are formed. Now, you can't see
the proteins here, because proteins are
very, very little. And for your
reference, if a cell is in the order of
nanometers, proteins are 10,000 times smaller
in the order of nanometers. So you cannot see them
with this microscope here. You have to use a
super microscope, which called electron microscope. And then if you
enlarge, ideally, you can see that proteins-- in this cartoon, of course-- are little dots of different
color and little strings that fill all the cytosol. And I'm talking about
proteins because they're a fundamental part of the cell. They are the
workers of the cell. They perform all the functions
that the cell needs to survive. And they're very
important in the case of neurodegenerative disorders,
which, as Meredith told you, has been one of the foci of
my 10 last years in the lab. And neurodegenerative
disorders actually cause dementia, cause the
loss of neuronal cells, which is manifested in the
patient with the lost of brain dementia. And dementia has been
defined by a Nature article as the approaching wave. Because in the next
30 years, the number of people affected by dementia
will increase exponentially. And according to the
World Alzheimer Report, today 50 million people
worldwide live with dementia. And this number will triple
in the next 30 years. This is an unsustainable
number as will be unsustainable for any economy, the
amount of money that will be spent for
these diseases, which will latent and overcome
2 trillions of dollars in today's dollars. And this fact was somehow
known already in 2007 by the US government
that defined a common enemy, dementia. However, something is wrong. Because although dementia
is the fifth cause of death worldwide-- and the end is
the most expensive disease to manage because it is a
chronic disease that requires continuous care for many years
of the patients that cannot do the very simple function
that a human being can do. Compared to other diseases like
cancer and HIV, for example, the funds for research
given to Alzheimer's, which is the most common cause of
dementia, and all the related diseases, is very, very low. So how can the US government
spend more than $260 billion on Alzheimer's care and give
less than 1% in research? Probably one of the simplest
explanation is disability. While patients affected by
cancer and HIV have been able to voice the need of funds to
fight for research and the need of funds to find the
cure for these diseases-- that we now have, in fact-- the patients affected
by dementia hideout. Dementia and Alzheimer's
is a disease of old age. And most of the time it's
mistaken as a normal aging process, which it's not. And family and caregivers are
often too tired and worn out to speak up. And this is not something
that is unique for you for the United States. This is a recent example of the
comparison on the annual cost for the UK economy on
dementia and cancer and what is given by the
UK to these two disorders. It's clear, not comparable. And adding reads just 1%
toward dementia research would make
breakthroughs possible. In this statement, as
some foundation-- in fact, if you look, again,
back in the US, in this graph, the comparison
between federal funding and change in mortality,
you see that the diseases like HIV that have received
more funding in years have been able to get huge
decreases in mortality. And it's incredible to see the
huge increase in the last five years of mortality for
Alzheimer's disease and the little money given. And what is more
disappointing and depressing is that hundreds of clinical
trials for Alzheimer's disease have been terminated because
the treatment was ineffective. And the situation is
even bleaker than this, because this is 2016. Today, many of these trials
ongoing have been terminated, some of them a
couple of months ago. And from a fundamental
researcher, like I am, a cell biologist, one
of the major causes of the failure of
these clinical trials is that we don't know enough
about the fundamental mechanism of these diseases. So until we know what happens at
the cellular level, ultimately molecular level, we will not
be able to devise a cure. But there is hope. In fact, in this graph, you
can see that in the last five years, the NIH budget for
Alzheimer and related disorders has tripled. And therefore, we hope
there will be more money not only for clinical
trials and so on and applied research but
also for fundamental research, that we study the
cause of this disease. Alzheimer's is one of
the most feared disease. And I think the
fear of this disease is represented by this slide. In 1995, an American
painter, William Utermohlen, was diagnosed with
Alzheimer's, and he was 61. And he never gave up his
passion and continued to paint until his brain, his
memory, completely failed him. And these portraits are
a unique representation of what happens in inner life,
the inner life of a person affected with
Alzheimer's and testify to the inexorable
progression of this disease. And if you look here, this is
his last painting in year 2000. And what is really disturbing is
that he lived seven more years until he died in 2007. So Alzheimer's disease
is a progressive and neurodegenerative
disease that was firstly identified by Alois Alzheimer,
a German doctor, in 1906. And what Alzheimer
did, he identified the pathological lesions that
were associated, that he found, actually, in the brain
of one of his patients, Mrs. Deter, age
55 when she died. And he identified two different
neuropathological lesions-- the tangles,
neurofibrillary tangles, which you can see here
in these dying neurons, the cell of the brain,
and these senile plaques that were outside the neurons. And what is interesting is that
these two different lesions are caused by the accumulation
of pathological proteins. The little tiny proteins
that I told you before, well, when they're accumulating these
lesions, they cause, somehow-- we don't know how exactly-- the death of the neurons and
the incredible loss of the brain tissue that you can see here in
the terminal stage of a patient affected with Alzheimer's. Now, one interesting thing that
I want to tell you is that all neurodegenerative
diseases-- all of them, Alzheimer's, Parkinson's,
ALS, Huntington's, the prion diseases-- are characterized by the
accumulation of misfolded, let's say, pathological
proteins in different areas of the brain, where they cause
these different lesions-- different proteins,
different area of the brain, different lesions. So all these diseases are
called protein conformational disorders. Why protein
conformational disorders? Because, as I told you,
when the proteins exit the endoplasmic
reticulum, you have to imagine them as a
string, as a ribbon, so you can fold them
in many different ways. However, only one folding, the
native folding of that protein, is functional. So only when the proteins reach
that native state they can make the function they're made for. What happens in
neurodegenerative disorders is that this protein, this
string, starts to misfold. And they can form what is
called disordered aggregates. So there are [INAUDIBLE]
that are aggregated that are non-functional. However, they can also
assume a different folding that allows this protein
to aggregate one together with the other one and to
form some huge aggregate that are called amyloid fibrils. And these aggregates not
only are non-functional but are also toxic. And they cause the
death of the neuron and the loss of
the brain tissue. Now, the best known of these
protein misfolding disorders are the prion disorders,
the Prion diseases, which are caused by the
misfolding and aggregation of a specific protein, which
is called the prion protein. Now, the difference between all
these other neurodegenerative diseases and the prion disorders
is that prion disorders are infectious. Being infectious means that
this disorder, these diseases, are transmitted between
individuals of the same species or between individuals
of different species, like you might recall,
like Meredith told you, in the case of the mad cow
disease that was transmitted to human beings after ingestion
of contaminated foodstuff. Now, I'm telling one thing
here that is strange, at least sounds strange. When you think of
an infection, you don't think of a protein,
this tiny little thing that is in cytosol. You think of a
virus, of a bacteria, of an organism that has some
sort of genetic material that can replicate in your
body or in pieces of your body and infect you. But prions are infectious. Why are they infectious? And this was worked out
by Stanley Prusiner that got the Nobel Prize in '97. In a recent interview
in The New York Times, Stanley Prusiner was defined
the heretical neurologist, because Stanley Prusiner
went against the dogma that was told to ask, to everybody,
that proteins are not infectious. And he proposed that prion
disorders are, in fact, infectious and that caused by an
infectious protein, the prion. This was the name he created. And he demonstrated
against the dogma and against many
of his colleagues that prions are
infectious because they exist in two different forms-- the normal form,
the cellular form, PRpC, and the pathological
form that is called PrPsc. And PrPsc, the
pathological form, is able to imprint the
misfolding on the cellular form in a now catalytic
conversion process that leads to the formation of
this huge amyloid aggregate. How this occurs is not known. But the
polymerization/nucleation model is the most accredited model,
and I have a cartoon there. You have the misfolded form is
stabilized in little aggregates that are called oligomers. Now, these oligomers
are able to recruit more and more of the normal
protein and misfolded, form the fibrils. The fibrils break. They form, again, the nucleation
oligomers that recruit the normal form, and this is a
continuous conversion process. Now, if this conversion process
would be limited to one cell, we lose one neuron. I think we lose many units. But the problem is that we
don't lose only one neuron. The problem is that
prions are able to spread like a virus and bacteria
from one cell to another. They enter the healthy
cell, and they start to seed the misfolding of the normal
protein that is continuously produced by the cell. So the question that
we wanted to answer, that we asked 10 years
ago in my lab, was, how do prions move from
one cell to another? And this is
particularly interesting if you think about the
infection from mad cow disease. This is an oral infection
most of the time. You ingest the
contaminated food stuff. The prion enters the gut. And then this red
nasty prion here-- they have to go to the brain. They cannot jump. They have to pass
necessarily-- they have to pass between
different cells before they reach the brain. And I don't have time
to go into details, but what we postulated 10 years
ago was that dendritic cells-- these very motile
cells that normally have to patrol the intestine--
would be able to take the prion and then give it to the
peripheral enteric system and then to peripheral
nervous system to the brain. Now, if you were a prion and
wouldn't move between cells, you naturally would
use a mechanism that cells use to
communicate to each other. So our prion moves. And the cells need to
communicate to each other. Because since the cell
theory was made and refined by Virchow [INAUDIBLE]
cellular, all cells come from other cells. It was clear that the original
proposal that the cell was an independent structure was
not working, because cells need to communicate
to the external media and need to communicate
with other cells in order to work together. So our cells communicate. And Diego has made a very
simple schematic here that tells us that
cells communicate by two fundamental mechanisms,
either directly by contact so they can exchange
things, or at a distance. And a distances is
kind of signaling, so these cells need to
communicate something to cells that are very far away. So this cell would secrete
a molecule, a protein, or an [INAUDIBLE] that would
be received by the distant cell that would react. Now, a way of distant
communication through secretion is represented by
the synapse, which is the connection that
neuronal cells, neurons, make with other neurons. But in this case, the distance
is covered by this long arm-- that Meredith told you-- that protrudes from one
neuron, [INAUDIBLE],, and then reaches the target
cell, another neuron, or a muscle cell, for example. And at this level,
he makes a junction. So the secretion occurs
at a very tiny distance, and this makes the communication
and distance between neurons to be very, very precise. Because the target
cell, it's just there. So at the synapse, the neurons
secrete a neurotransmitter, and then these cells receive
the neurotransmitter and react. So in fact, when we were trying
to understand how prions move, it was proposed that prions
move through secretions at the level of the synapse
with the secretion and uptake. However, in the lab, we
decided to see how could prions move between dendritic cells-- these peripheral
cells-- to the neurons. So what we did in the lab,
we took dendritic cells from a mouse. We filled them with a
fluorescent prion particle, red dots, and we co-cultured the
cells, the two type of cells, in a same dish, and looked
under the microscope what was happening. And what was happening
was mind-blowing. Because what we saw, indeed,
was that these two different cells-- the neuron and
the dendritic cell-- were establishing a sort
of channel between them. And through this channel,
the prion would move. And here you can see it well in
these still images in which you can see a red dots coming
from the dendritic cell, reaching the neurite
of this neuron here. And we went on, and we found
that between neuronal cells, these channels also exist. And this channels are
full of prion proteins, as you can see here
in this live movie. And this was an animation. And in this movie,
when I start, you can see that this particle here,
these are two cells connected by a channel-- this one here. And the particle
moves from one cell, jumps on a very thin
channel that you don't see because the
resolution is not enough, and enter the connected cell. So these channels-- ah,
Meredith spoiled all my talk-- are called tunneling nanotubes. But tunneling nanotubes
were discovered in cultures between cells by [INAUDIBLE]. And he proposed that these
were very thin and fragile open tubular connections,
allowing communication between the cells, and
allowing the passage of many cellular components. Now, this proposal was not
well-accepted by the field, because it was going
against the dogma that cells do not open up to
each other to communicate. They do send signals or
they established synapses at least in our body. But I thought this
was absolutely true, because we could see
this channel forming under the microscope. And we could see
that prions were passing through this channel. So for the last
10 years, we have been working in trying to
understand how tunneling nanotubes have formed,
what are the molecules, and we were able to demonstrate
that as was proposed here, we demonstrated that there are
open connections very different from different protrusions. And they allow the
communication between cells. And the passage of these
red dots here, that are not prions, but are
entire mitochondria-- the power station of
the cell, organelles-- are exchanged between them. Wow. So tunneling nanotubes
are a direct mechanism of communication between
cells and a major highway for the spreading of prions. Why am I telling
you about prions? This is a very rare
disease and not many people get infected
by prions today. I'm telling you about prions
because in the last 15 years, evidence from many different
labs, including ours, have shown that non-infectious
amyloid proteins that accumulate in other,
more frequent-- this is like Alzheimer's,
Abeta, and Tau, and Parkinson's, [INAUDIBLE]----
share many properties with prions. In fact, they can exist in
different conformations, like prions do. They can direct template
conformation of changes of the normally
folded counterpart and form these amyloid fibrils. And they can, therefore,
propagate the misfolding. So the question we
wanted to ask in the lab is, are they capable to
transfer between cells? And there is very good
evidence in literature from the early observation
of Heiko Braak, a fantastic neuropathologist, that by
observing the postmortem brain of patients affected
by different diseases like Alzheimer's, Parkinson's,
ALS, Huntington's, and so on, looking at the brain
of these patients, he discovered that each of
these different diseases would start in a specific
area of the brain that would be different in
the different diseases. But the pathology, that is
the aggregate precipitation that he could see in the
brain, the pathology, would spread in a
predictable way, because he would spread through
connectivity, through area that we know now they
are interconnected. So these observations
would fit very well with the spreading of misfolded
proteins in the brain. So the disease will spread
like prions, like an infection. And this hypothesis of Braak
has been recently confirmed in living patients, using
very advanced PET scanning and functional MRI scanning that
have led these researchers-- this is one example,
very recent-- to identify in the brain of the
living patient with Alzheimer's the Tau aggregate. It's the same Tau that
Louis Alzheimer was looking in the brain of Madame Deter. And what they found
is that they have been able to correlate the
amount of misfolded Tau in the brain of these patients
with the loss of connectivity with loss of function
of the brain itself. So we asked how
these Tau aggregates move between each other. Are TNT-- tunneling
nanotubing-- involved? So we are cell biologists. We work with cells. So we took some neuronal
cells, not from this brain, but from human neuron
cells, by the way. And we expressed the Tau protein
in the cells, the normal Tau protein. The normal Tau protein in green,
when the Tau protein is normal, you don't see it. It's very little. You see a general diffuse
signal that is green. Then we add that to this
culture the aggregate of a misfolded Tau in red. And then, what we saw is this. Now, here are the bad
aggregated [INAUDIBLE] in red that we added. And here in the bottom, there
is the culture of a neuron. Now, these neurons are
expressing the normal folded Tau protein. So this protein is diffuse. You have a diffuse signal. When I start the
movie, you will see that these diffuse signals-- the green signals--
start to form spots. And you can see it very
well now, very strong. And these spots are diffusing
in the whole culture. In three days, the whole
culture is full of these spots. So basically, what we could
reproduce in this culture is this spreading, the
seeding and the spreading, of Tau from one neuron
to the order in culture. And then when we looked
at the higher resolution, we could see that this
Tau aggregate would spread through this tunnel. A similar thing, we
went to Parkinson's. Parkinson's is an
older disease in which there are misfolded aggregates. And Parkinson's is
very interesting, because in this case,
it's really very evident that the symptomatology
of the disease progresses from periphery
with peripheral symptoms, that is, the inability to
coordinate, to move, et cetera, to the central
symptom that is dementia, which is the last symptom. And this is very well
represented by the Braak stage. In fact, at the beginning,
in Parkinson's, there's accumulation of these misfolded
proteins only in the brain stem and in the nuclei that
coordinate the movement. And then later on
in life, the disease accumulates in the cortex,
and you have dementia. And these pathological lesions
the case of Parkinson's are caused by another protein that
is called alpha-synuclein, and there is evidence in
literature that alpha-synuclein which form these aggregates-- they are called Lewy
bodies and Lewy neurites-- are moving between neurons
in the brain of patients. I can tell you more about
that in the questions. So what we did, we
did the similar thing. We did co-culture, and we could
see that these red synuclein aggregate or these green
synuclein aggregates were inside of
tunneling nanotube. And we could see similar
things in the mouse brain slice, in which you can
see these red dots moving between these two neurons. It's not very clear,
the movie, but you can see that they're moving
through these thin connections, which we presume are
tunneling nanotubes. So basically, our data
support the hypothesis that tunneling
nanotubes contribute to the spreading of different
neurodegenerative diseases by allowing the transfer
of misfolded protein from the diseased
cell to naive cells where conversion would
occur and therefore they would propagate the pathology. But why would cells do this? Why would cells send a toxic
aggregate to another cell, to a healthy cell? This is suicide, right? So what happens? And what we found
is, in fact, when you have an aggregate
in a cell, a cell would send the aggregate to
the lysosome, to the cleaners. And then the lysosome,
normally the aggregate would be disposed. But if you have a prion
phenomenon in which you have a continuous accumulation
of these aggregates, what happens, in fact,
is that the lysosome are overwhelmed, overloaded
with these misfolded aggregates. And then they stop functioning. And so what we found is
that the whole lysosome with the aggregate inside is
transmitted between the two cells through a
tunneling nanotube. It's like this cell that
does the aggregate is asking for help to a healthy
cell and saying, well, I cannot do anything anymore. Can you help? Well, they can't help. Because what happens
when the lysosomes get to the healthy cell? What happens is that
these broken lysosomes allow the exit of the
aggregate from the lysosome. And this aggregate-- this
pathological aggregate-- would meet the diffuse
protein, the normal protein, and would start the aggregation. And this is the way this
propagates between cells. And the last thing I
want to tell you about-- one last thing about
this phenomenon-- is that any of these
aggregated-- in prion disorder, Alzheimer, any aggregated
protein that we give to normal neurons
would decrease the formation of tunneling nanotubes. And then this would allow
the spreading of the disease to healthy cells. So we suppose, but
we don't know yet, that there is a common
mechanism to all aggregates that would allow the formation
of tunneling nanotubes. And therefore, we believe
the tunneling nanotubes could be a potential
therapeutic target to stop the progression of
neurodegenerative disease. And we are looking into
testing some molecules, but we are very far away. OK. Now I told you this nice
story and nice movies. But this is done
totally in vitro. Is there any relevance
for the progression of neurodegenerative diseases? We cannot base these on
observation made between neurons. So the question is, do TNT-- tunneling nanotubes--
exist in vitro? This is not a trivial question. This is a very
complicated question. Because the brain is a
very complex network. And Jeff Lichtman can
tell you everything. I'm not a neuroscientist. I'm a cell biologist. But what we know is that in
the brain of a human being, there are at least
100 billion neurons. And these 100 billion
neurons, each of them can make contact with
thousands of other neurons, making trillions of synapses. In this huge,
complicated wiring that contains all our emotion,
our knowledge, our thought, the way we walk,
the way we sleep, everything is encoded
in these networks, that changes also with time. So no two brains are the same. And this correspondence
between the physical connection and the action,
the brain function, was proposed and discovered
at the end of 19th century by Ramon y Cajal. For example, in
this wiring diagram here, he proposed then when
you have a stimuli coming from the skin and with the
sensory neuron termination, this neuron will contact another
neuron in the spinal cord. And this neuron from the spinal
cord to a synaptic connection would contact other
neurons, reach the cortex, and then from the
cortex, the stimuli-- the same stimuli-- is passed
down through the spinal cord through the
[INAUDIBLE] neuron that will then reach your
muscle and get a reaction to the sensory stimuli. But this is a very
simple wiring. So just to give you a
hint of the complication, these are only 300
neurons that have been wired in the brain [INAUDIBLE]. I told you that we have
billions of neurons. So how can we identify
tunneling nanotubes in these complex
networks of connections? And this brings me to
my Radcliffe project, which is a project in
collaboration with Jeff Lichtman-- he is here-- carried on by a fantastic
PhD student, Diego. He's also here. Thank you for being here. And three fantastic
undergraduates, my Radcliffe partner,
Leo, Eric, and Alex, who should also be here. Oh, they're there. So what Jeff is interested in-- he's a fantastic neurobiologist. he's interested in understanding
the whole [INAUDIBLE],, the whole connection in the
brain, how cells in the brain wire to each other. And he has devised many
different ways to look at it. But the most interesting for
us is a connectomic approach based on serial scanning
electron microscopy. Why? This is the same
electron microscopy that I told you is
able to visualize the tiny little
proteins in the cell. So Jeff has set up in his lab
these serial scanning electron microscopy that
he's able to look at nanometer resolution in
a digitalized piece of brain by imaging different sections of
the brain that are mounted one after the other so that you can
see each cell, each connection, each synapse, each vesicle,
each protein inside the vesicle. So I've taken a video
from Jeff's website to explain what is
this connectomic. And I don't think I
can speak on this video because it's really
very difficult. But you can ask him,
how does he work? Just for the beauty
of it, because it's a very beautiful technique. So once you have taken a
brain of a mouse in this case, and you fix it,
and you stain, you start cutting it automatically. And then this very
thin slice here, these thin slices are collected
in a film tape, which is then cut in different slices. And then each slice is imaged
of higher and higher, higher resolution. So you have the impression
that you go inside the brain, and then you can see at
this high resolution-- you can see everything is there. You can see all the
connections, everything. And you can segment
them-- and that's what Diego and the
students are doing-- until you get to the volume, a
very tiny volume of the brain. You can open up,
expand this volume, and reconstruct in
3D each connection at the synaptic level. Wow. That's wow, really. [LAUGHTER] What we decided
to do is to look, to use this of
connectomic approach to look for tunneling nanotubes. Because then we can see
this thin connection because we can see everything. And we decided to do
it in the cerebellum, for various reasons,
but the cerebellum is-- at birth, in a mouse, some
cells are not mature enough, finally mature, and so they
don't establish the synapse. But what these cells
do, these red cells, are able coordinately to
migrate or in [INAUDIBLE].. But they don't have connections. So how do they do
that altogether? So we proposed, we
postulated, maybe they are connected to
tunneling nanotubes. So Diego went to Jeff's lab. He prepared these with
the help of his lab, prepare this volume, this tiny
volume of the mouse brain, and started to segment all the
cells, all the connections, in this brain. OK. And after almost two
years of segmentation-- this is a tedious thing to
do, but it's very rewarding when you find the connection. And the work of many students--
of Diego and many students-- we found several
connections in several cells in the developing brain. And, of course, this is very
interesting and unexpected. Even to us when we
started, we said, well, let's try, because you have
found something in vitro. Until you find something
in vivo, you don't know. And so, it goes
against the dogma. It goes against the
dogma that said, do not open up to each other. And they do it. Apparently they
do it in a brain. So in order to convince
our peers and ourselves that this is true, we are
doing a lot more experiments. This doesn't finish here. There's lot more to do,
but it's a good start. And of course, it's a good
start to answer the question, are they also exchanging
this connection amyloid proteins, which
is what we want to know. Let me go back in history,
though I'm five minutes off. I told you that Cajal
worked out all [INAUDIBLE],, worked how through synaptic the
cells connect to each other. However, at the
same time, there was an Italian, anatomist
Camillo Golgi, who also got the Nobel
Prize in 1906 with Cajal. But they didn't
talk to each other, Camillo Golgi was
old fashioned, and he was convinced that, in fact,
the neurons would somehow form a reticulum. The neuronal cell would be
connected in a reticulum to each other. So each piece of brain
would work together because the cell will not
communicate to the synapse but will be basically
one body, one reticulum. Because he could see this
staining that he was using, diffusing from one
cell to another. Now we know that
Cajal was right. But in light of what I
told you, the question is, was Camillo Golgi maybe
somehow right as well? And then, I want to tell you
my little secret that is not my secret, but it's
a secret that I borrow from this
book, The Little Prince, that has accompanied
me since I was a kid. And these little secret these
very simple and tells you, "It is only with a heart
that one can see rightly. What is essential is often
invisible to the eye." And this is the most
important slide. This is thanks to
my lab that are giving all their heart in this
work, that this is possible. Thanks to all the student
postdoc researchers that I have in Paris,
that share with me the passion for science. They understand that the
way, the path to discoveries, is made of very small steps
and very few aha moments that will fill the rest of
your life, of course. And thank you to Diego who is
somewhere here, my partner, and of course,
this wouldn't have been possible without
the collaboration of Jeff Lichtman, who has opened
the door to his lab to this crazy project. And thank you very much
for your attention. [APPLAUSE] [MUSIC PLAYING]
