The life unfolding inside your cells, revealed in 3D
-
0:01 - 0:05Trying to understand life
without clearly watching it in action -
0:05 - 0:08is like an alien species trying
to understand the rules of a football game -
0:08 - 0:10from just a few snapshots.
-
0:10 - 0:12We can learn a lot from these images.
-
0:12 - 0:15For example, there's players
on and off the field. -
0:15 - 0:16There's a band.
-
0:16 - 0:20There's even cheerleaders
having a great time watching the game. -
0:20 - 0:23And of course, despite learning
all of this information -
0:23 - 0:26from watching these pictures,
-
0:26 - 0:28we still cannot piece together
the rules of the game. -
0:28 - 0:30In order to be able to do that,
-
0:30 - 0:32we need to actually
watch the game in action. -
0:33 - 0:36Much of what we know about how life works
-
0:36 - 0:38comes from watching these snapshots.
-
0:38 - 0:42Scientists have been able to figure out
a lot by looking at similar snapshots, -
0:42 - 0:46but ultimately, for them
to understand how life works, -
0:46 - 0:48they need to actually watch it in action.
-
0:48 - 0:51And this is essentially
where life happens, -
0:51 - 0:55is trying to understand
how the fundamental unit of life works. -
0:55 - 0:57And to be able to watch this,
-
0:57 - 1:00we need to be able
to understand how life is. -
1:01 - 1:03Compared to this ant,
-
1:03 - 1:07a human cell is about a hundred million
times smaller in volume. -
1:07 - 1:10Do you see the cell
that's right next to this ant? -
1:10 - 1:11It's right there.
-
1:11 - 1:12To be able to watch this cell,
-
1:13 - 1:16we need to make the invisible visible,
-
1:16 - 1:18and we do this by building microscopes.
-
1:18 - 1:19Not these microscopes;
-
1:19 - 1:22the ones that we build
look something like this. -
1:22 - 1:25It helps that I'm part
of a paparazzi -- well, of sorts. -
1:25 - 1:27Instead of taking pictures of people,
-
1:27 - 1:30I'm more interested
in taking pictures of famous cells. -
1:30 - 1:34Well, my own career path
up until this moment in time -
1:34 - 1:35has been pretty windy,
-
1:35 - 1:40starting with my first childhood obsession
and continued passion in computer science, -
1:40 - 1:44which took a sharp transition
to looking at engineering, -
1:44 - 1:46and more recently,
-
1:46 - 1:50a very sharp transition
to trying to understand cell biology. -
1:51 - 1:54Now, it's this combination of disciplines
-
1:54 - 1:56that has led me to where I am today.
-
1:56 - 1:59I'm able to carry out
interdisciplinary research -
1:59 - 2:00with one clear goal.
-
2:00 - 2:04And the idea is to be able to advance
innovation and discovery -
2:04 - 2:07by bringing together experts
from these different disciplines -
2:07 - 2:11to be able to work together
and solve problems that each of us can't. -
2:12 - 2:15Now, we're interested
in understanding the cell. -
2:15 - 2:16The cell ... what is it?
-
2:16 - 2:18Well, it's the fundamental unit of life.
-
2:18 - 2:21Simply put, it's just a bag.
-
2:21 - 2:24It's a bag that has trillions
of inanimate molecules, -
2:24 - 2:27whether it's proteins,
carbohydrates, lipids or fat. -
2:27 - 2:29And it turns out,
over the past half a century, -
2:29 - 2:32molecular biologists and biochemists
have figured out ways -
2:32 - 2:34to make these proteins glow.
-
2:35 - 2:37They light up just like fireflies.
-
2:38 - 2:40Now, microscope developers
have been able to make -
2:40 - 2:41better and better instruments
-
2:41 - 2:44to be able to capture this light
emitted from these molecules, -
2:44 - 2:48and computer scientists and mathematicians
have been able to understand -
2:48 - 2:51the signals that are being recorded
from the cameras. -
2:51 - 2:54And by bringing these tools together,
-
2:54 - 2:58we're actually being able to understand
the organization of these molecules -
2:58 - 2:59inside of these cells,
-
2:59 - 3:02understand how that changes over time,
-
3:02 - 3:05and that's essentially
what we're interested in, -
3:05 - 3:07trying to understand life at its essence.
-
3:08 - 3:10So we want to go from imaging life,
-
3:10 - 3:13which has traditionally
been confined to two dimensions, -
3:13 - 3:16to being able to image life
in three dimensions. -
3:16 - 3:19So how do you make a two-dimensional image
into a three-dimensional image? -
3:19 - 3:21Well, turns out
it's pretty straightforward. -
3:21 - 3:24We just collect a series
of two-dimensional images -
3:24 - 3:25as we're moving the sample up and down,
-
3:25 - 3:28and then we stack the images
on top of each other -
3:28 - 3:30and create a three-dimensional volume.
-
3:30 - 3:33The problem with this approach
is that traditional microscopes, -
3:33 - 3:35they dump way too much energy
into the system. -
3:35 - 3:38That means that this cell
that you see over here, -
3:38 - 3:41it's experiencing a lot of light toxicity,
-
3:41 - 3:42and that's a problem.
-
3:43 - 3:45Let me explain that a little bit better.
-
3:45 - 3:47For example,
-
3:47 - 3:50let's say that on this planet,
life evolved under just one sun, yes? -
3:51 - 3:54Now, let's say I wanted to watch
the shoppers on this street -
3:54 - 3:56to understand their shopping habits:
-
3:56 - 3:58how long they linger
in front of stores window shopping, -
3:58 - 4:00how many stores they go into
-
4:00 - 4:02and how long they spend
inside of each of the stores. -
4:02 - 4:06And if I was sitting down
at a coffee shop just people-watching, -
4:06 - 4:08many wouldn't even notice
that I'm watching them. -
4:08 - 4:09Now, what if all of a sudden
-
4:09 - 4:11I was shining the equivalent
of what is, say, -
4:11 - 4:17the light or the sunlight from about five
or, say, 10 different suns? -
4:17 - 4:19Would they still behave
as they normally did? -
4:20 - 4:23Would they still linger outside
for just as long? -
4:23 - 4:26Can I really believe
that their behavior hasn't been altered -
4:26 - 4:30as a consequence of being exposed
to this much sunlight? -
4:30 - 4:31No.
-
4:31 - 4:33Most microscopes these days,
-
4:33 - 4:35and conventional microscopes,
-
4:35 - 4:39have been able to dump between
10 to 10,000 times the sunlight -
4:39 - 4:42that we're exposed to on this planet,
where life actually evolved. -
4:43 - 4:45And because of this,
-
4:45 - 4:48well, turns out I'm part
of the cell paparazzi, -
4:48 - 4:51so we need to be very careful
in terms of how much light -
4:51 - 4:52we actually put into the cell.
-
4:53 - 4:55Otherwise, we might end up
with a deep-fried cell. -
4:56 - 4:57And, turns out,
-
4:57 - 5:01there's really nothing natural
about trying to watch a damaged cell -
5:01 - 5:04whose behavior has been
significantly altered. -
5:05 - 5:09Well, let's take this cell for example.
-
5:09 - 5:11It's sitting on a piece of glass.
-
5:11 - 5:12You see the spots everywhere?
-
5:12 - 5:15Those spots represent molecular machines
-
5:15 - 5:17that are assembling
on the surface of the cell -
5:17 - 5:22in order to be able to shuttle food
from outside the cell into the cell. -
5:22 - 5:25Our lab uses something called
the lattice light sheet microscopy, -
5:25 - 5:28which generates a very,
very thin sheet of light, -
5:28 - 5:30paying attention not to damage the cells
-
5:30 - 5:32or not to put too much light
into the system. -
5:32 - 5:34And when we do this,
-
5:34 - 5:38we're able to watch the dynamics
of that process for much longer -
5:38 - 5:40without really stressing out these cells.
-
5:41 - 5:43We've used this microscopy
technique and tools -
5:43 - 5:46to be able to understand
how viruses infect cells. -
5:46 - 5:49In this example, we've exposed
the cell to rotavirus. -
5:49 - 5:54It's an extremely contagious pathogen
that kills over 200,000 people every year. -
5:54 - 5:57And by watching these molecules,
these virus particles, -
5:57 - 5:59how they diffuse
on the surface of the cells, -
5:59 - 6:02we can actually understand
the rules that they're playing by. -
6:02 - 6:04And when we understand these rules,
-
6:04 - 6:05we can start to outsmart them,
-
6:05 - 6:07whether through
intelligent drug therapies, -
6:07 - 6:11to be able to mitigate, manage
or even prevent the virus -
6:11 - 6:13from binding into the cell
in the first place. -
6:14 - 6:17Now, we've made the invisible visible,
-
6:17 - 6:18but the question remains:
-
6:18 - 6:20When can we believe what we actually see?
-
6:20 - 6:23Everything I've shown you
up until this point -
6:23 - 6:27has been a cell that's been held prisoner
on a piece of glass or in a petri dish. -
6:27 - 6:31Well, it turns out that cells didn't
really evolve on a piece of glass. Right? -
6:31 - 6:32They didn't evolve in isolation,
-
6:33 - 6:35and they didn't evolve
outside their physiological context. -
6:35 - 6:38To truly understand
cells' natural behavior, -
6:38 - 6:44we need to able to watch them in action
where actually is their home turf. -
6:44 - 6:48So, let's take a look
at this complex system. -
6:48 - 6:51This is a developing zebra fish embryo,
-
6:51 - 6:54where you're looking at cells
that are organizing themselves -
6:54 - 6:57in order to form tissues,
in order to form organ systems. -
6:57 - 7:00And when we watch the movie again,
you'll see that at about 20 hours, -
7:00 - 7:03you start to form the eye
and the tail of the zebra fish. -
7:03 - 7:05Now, we can watch this,
not in this low resolution, -
7:05 - 7:08we can watch this in exquisite detail,
-
7:08 - 7:11and we want to be able
to watch this in three dimensions -
7:11 - 7:13over the course of minutes, seconds,
hours or even days. -
7:14 - 7:17So the problem with these complex systems
-
7:17 - 7:19is that we scramble the light,
-
7:19 - 7:22or they scramble the light
that we actually shine onto them, -
7:22 - 7:25which causes us to record
very blurry images. -
7:25 - 7:29And it turns out that astronomers
have had a similar problem, -
7:29 - 7:30but for them, the problem comes
-
7:30 - 7:34when they're trying to record
the light from distant stars -
7:34 - 7:36on telescopes that are ground-based.
-
7:37 - 7:40The problem is, when the light travels
thousands of light years -
7:40 - 7:43and it hits our turbulent
atmosphere all of a sudden, -
7:43 - 7:44the light gets scrambled.
-
7:45 - 7:47They've also, luckily, figured out
a solution to this -
7:47 - 7:49for over half a century.
-
7:49 - 7:52What they do is they generate
an artificial star -
7:52 - 7:54at about 90 kilometers
above the Earth's surface, -
7:54 - 7:56and they use that light,
-
7:56 - 8:00which passes through the same turbulent
atmosphere as the distant star's light, -
8:00 - 8:03and they're able to understand
how the light is getting scrambled, -
8:03 - 8:05and they take a mirror
that can change its shape -
8:05 - 8:08in order to compensate
or undo that scrambling. -
8:08 - 8:10So what we've done is
we've taken those ideas -
8:11 - 8:13and we've implemented that
with our microscope system. -
8:13 - 8:14And when you do that,
-
8:15 - 8:18you can more or less unscramble
the complexity of the scrambling -
8:18 - 8:20and the fuzziness that's happening
-
8:20 - 8:22as a consequence of complex systems.
-
8:22 - 8:24And we do this in zebra fish.
-
8:24 - 8:28We like zebra fish because,
like us, they're vertebrates. -
8:28 - 8:30Unlike us, they're mostly transparent.
-
8:30 - 8:33That means that when
we shine light on them, -
8:33 - 8:36we can watch the cellular
and the subcellular dynamics -
8:36 - 8:37with exquisite detail.
-
8:37 - 8:39Let me show you an example.
-
8:40 - 8:44In this video, you're watching the spine
and the muscle of a zebra fish. -
8:44 - 8:48We can look at
the organization of the cells -- -
8:48 - 8:51hundreds of cells
in this particular volume -- -
8:51 - 8:54in the presence and absence
of adaptive optics. -
8:54 - 8:55Now, with these tools,
-
8:55 - 8:59we can watch more clearly
than we've ever been able to before. -
9:01 - 9:02And in a very specific example,
-
9:02 - 9:05looking at how the eye develops
in the zebra fish, -
9:05 - 9:09you can really see the commotion inside
of this developing zebra fish embryo. -
9:09 - 9:12So you can see the cells
that are dancing around. -
9:12 - 9:15In one example, you see
how the cell is dividing. -
9:15 - 9:16In another example,
-
9:16 - 9:19you see cells trying to get places
and squeezing past another cell. -
9:20 - 9:24And in the last example, you see a cell
being completely rowdy to its neighbors -
9:24 - 9:25by just punching its neighbors.
-
9:25 - 9:26Right?
-
9:27 - 9:32This technology really enables us
to watch deeper and more clearly, -
9:32 - 9:35almost as if we're watching
single cells on a piece of glass -
9:35 - 9:37where they've been held prisoner.
-
9:37 - 9:40And to demonstrate the promise
that this technology holds, -
9:40 - 9:43we've partnered with some of the best
scientists from around the world. -
9:43 - 9:46And we've started to ask
a range of fundamental questions -
9:46 - 9:48that we're starting to work on
right now together. -
9:48 - 9:51For example, how does cancer
spread through the body? -
9:51 - 9:54In this example, you're looking
at human breast cancer cells -
9:54 - 9:56that are basically kind of migrating,
-
9:56 - 9:59where they're using the blood vessels
that are shown in magenta. -
9:59 - 10:02They're basically using
these blood vessels as highways -
10:02 - 10:03to move about the cabin.
-
10:03 - 10:06You can basically see them
squeezing through the blood vessels. -
10:06 - 10:09You can see them rolling
where there's enough space. -
10:09 - 10:12And in one example, well, you see
what looks like Ridley Scott's trailer -
10:12 - 10:13for the next "Alien" movie.
-
10:14 - 10:17This cancer cell is literally trying
to claw its way out of the blood vessel -
10:17 - 10:19in order to invade
another part of the body. -
10:22 - 10:24In the last example I'm going to show you,
-
10:24 - 10:26we're trying to understand
how the ear develops. -
10:26 - 10:30In this case, we were completely
upstaged by crawling neutrophils. -
10:30 - 10:33These immune cells are basically
on patrol all the time. -
10:33 - 10:35Basically, they don't get any time off.
-
10:35 - 10:38They're working constantly to understand
whether there's stranger danger, -
10:38 - 10:41trying to understand
whether there's an infection. -
10:41 - 10:44They're sensing the environment,
constantly moving around. -
10:45 - 10:49Now, we can watch these images
and these movies -
10:49 - 10:53in greater detail than has ever
been possible before in our time -
10:53 - 10:54up until now.
-
10:54 - 10:57Now, as with all new technologies,
-
10:57 - 10:59new capabilities come with new challenges,
-
10:59 - 11:03and for us, the big one
is how we handle the data. -
11:03 - 11:06These microscopes generate a ton of data.
-
11:06 - 11:10We generate anywhere from
one to three terabytes of data per hour. -
11:10 - 11:15To put that into context: we're filling up
two million floppy disks every hour, -
11:15 - 11:17for our more experienced audience members.
-
11:17 - 11:19(Laughter)
-
11:20 - 11:22Roughly equal, then, to about 500 DVDs,
-
11:22 - 11:25or to put things into
better context for the Gen Z, -
11:25 - 11:29that's about a dozen iPhone 11s
that I'm filling up every hour. -
11:31 - 11:33We have a ton of data.
-
11:33 - 11:35We need to find new ways
to be able to visualize this. -
11:35 - 11:37We need to be able to find new ways
-
11:37 - 11:40to be able to extract
biologically meaningful information -
11:40 - 11:41from these data sets.
-
11:41 - 11:42And more importantly,
-
11:42 - 11:45we want to make sure that we can put
these advanced microscopes -
11:45 - 11:48into the hands of scientists
from all around the world. -
11:48 - 11:52And we're giving the designs
of these microscopes for free. -
11:52 - 11:53But the key important part is,
-
11:54 - 11:56we need to collaborate even more
to make an impact. -
11:56 - 11:58We're bringing together scientists
-
11:58 - 12:01who can develop new
biological and chemical tools. -
12:01 - 12:04We're working together
with data scientists -
12:04 - 12:05and instrumentation scientists
-
12:05 - 12:08to be able to build and manage the data.
-
12:08 - 12:11And because we're giving
these instruments out for free -
12:11 - 12:14for all academic and nonprofits,
-
12:14 - 12:17we're also building advanced
imaging centers to house them, -
12:17 - 12:20to be able to bring together the group
of people that are microscopists, -
12:20 - 12:23that are the biologists
and the computational people, -
12:23 - 12:26and to build a team that's able
to solve the types of problems -
12:26 - 12:28that each of us individually cannot.
-
12:28 - 12:30And thanks to these microscopes,
-
12:30 - 12:32the frontier of science is open again.
-
12:32 - 12:33So let's take a look together.
-
12:34 - 12:35Thank you.
-
12:35 - 12:38(Applause)
- Title:
- The life unfolding inside your cells, revealed in 3D
- Speaker:
- Gokul Upadhyayula
- Description:
-
To understand how life works, you need to watch it in action, says bioimaging scientist Gokul Upadhyayula. Taking us down to the cellular level, he shares the work behind cutting-edge microscopes that capture and record, in three dimensions, the complex behaviors of living organisms -- from infecting cancer cells to crawling immune cells -- and what they're revealing about the dynamics of biology. Watch life unfold before your eyes with the incredible visuals in this talk.
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 12:51
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Camille Martínez edited English subtitles for The life unfolding inside your cells, revealed in 3D | ||
Camille Martínez edited English subtitles for The life unfolding inside your cells, revealed in 3D | ||
Joseph Geni edited English subtitles for The life unfolding inside your cells, revealed in 3D | ||
Joseph Geni edited English subtitles for The life unfolding inside your cells, revealed in 3D | ||
Joseph Geni edited English subtitles for The life unfolding inside your cells, revealed in 3D |