5 challenges we could solve by designing new proteins
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0:01 - 0:05I'm going to tell you about the most
amazing machines in the world -
0:05 - 0:07and what we can now do with them.
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0:07 - 0:09Proteins,
-
0:09 - 0:11some of which you see inside a cell here,
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0:11 - 0:14carry out essentially all the important
functions in our bodies. -
0:15 - 0:17Proteins digest your food,
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0:17 - 0:19contract your muscles,
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0:19 - 0:20fire your neurons
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0:20 - 0:22and power your immune system.
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0:22 - 0:24Everything that happens in biology --
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0:24 - 0:26almost --
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0:26 - 0:27happens because of proteins.
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0:28 - 0:32Proteins are linear chains
of building blocks called amino acids. -
0:32 - 0:36Nature uses an alphabet of 20 amino acids,
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0:36 - 0:38some of which have names
you may have heard of. -
0:39 - 0:42In this picture, for scale,
each bump is an atom. -
0:43 - 0:48Chemical forces between the amino acids
cause these long stringy molecules -
0:48 - 0:51to fold up into unique,
three-dimensional structures. -
0:52 - 0:53The folding process,
-
0:53 - 0:55while it looks random,
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0:55 - 0:57is in fact very precise.
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0:57 - 1:01Each protein folds
to its characteristic shape each time, -
1:01 - 1:05and the folding process
takes just a fraction of a second. -
1:06 - 1:08And it's the shapes of proteins
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1:08 - 1:12which enable them to carry out
their remarkable biological functions. -
1:13 - 1:14For example,
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1:14 - 1:17hemoglobin has a shape
in the lungs perfectly suited -
1:17 - 1:19for binding a molecule of oxygen.
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1:20 - 1:22When hemoglobin moves to your muscle,
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1:22 - 1:24the shape changes slightly
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1:24 - 1:26and the oxygen comes out.
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1:27 - 1:29The shapes of proteins,
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1:29 - 1:31and hence their remarkable functions,
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1:31 - 1:37are completely specified by the sequence
of amino acids in the protein chain. -
1:37 - 1:41In this picture, each letter
on top is an amino acid. -
1:43 - 1:45Where do these sequences come from?
-
1:46 - 1:50The genes in your genome
specify the amino acid sequences -
1:50 - 1:52of your proteins.
-
1:52 - 1:56Each gene encodes the amino acid
sequence of a single protein. -
1:58 - 2:01The translation between
these amino acid sequences -
2:01 - 2:04and the structures
and functions of proteins -
2:04 - 2:06is known as the protein folding problem.
-
2:06 - 2:08It's a very hard problem
-
2:08 - 2:11because there's so many different
shapes a protein can adopt. -
2:12 - 2:14Because of this complexity,
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2:14 - 2:17humans have only been able
to harness the power of proteins -
2:17 - 2:20by making very small changes
to the amino acid sequences -
2:20 - 2:22of the proteins we've found in nature.
-
2:23 - 2:27This is similar to the process
that our Stone Age ancestors used -
2:27 - 2:30to make tools and other implements
from the sticks and stones -
2:30 - 2:32that we found in the world around us.
-
2:33 - 2:38But humans did not learn to fly
by modifying birds. -
2:39 - 2:41(Laughter)
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2:41 - 2:47Instead, scientists, inspired by birds,
uncovered the principles of aerodynamics. -
2:47 - 2:52Engineers then used those principles
to design custom flying machines. -
2:52 - 2:53In a similar way,
-
2:53 - 2:55we've been working for a number of years
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2:55 - 2:59to uncover the fundamental
principles of protein folding -
2:59 - 3:03and encoding those principles
in the computer program called Rosetta. -
3:04 - 3:06We made a breakthrough in recent years.
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3:07 - 3:11We can now design completely new proteins
from scratch on the computer. -
3:12 - 3:14Once we've designed the new protein,
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3:15 - 3:19we encode its amino acid sequence
in a synthetic gene. -
3:20 - 3:22We have to make a synthetic gene
-
3:22 - 3:24because since the protein
is completely new, -
3:24 - 3:29there's no gene in any organism on earth
which currently exists that encodes it. -
3:30 - 3:34Our advances in understanding
protein folding -
3:34 - 3:36and how to design proteins,
-
3:36 - 3:39coupled with the decreasing cost
of gene synthesis -
3:39 - 3:43and the Moore's law increase
in computing power, -
3:43 - 3:48now enable us to design
tens of thousands of new proteins, -
3:48 - 3:50with new shapes and new functions,
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3:50 - 3:51on the computer,
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3:51 - 3:55and encode each one of those
in a synthetic gene. -
3:56 - 3:58Once we have those synthetic genes,
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3:58 - 3:59we put them into bacteria
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4:00 - 4:03to program them to make
these brand-new proteins. -
4:03 - 4:05We then extract the proteins
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4:05 - 4:09and determine whether they function
as we designed them to -
4:09 - 4:10and whether they're safe.
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4:12 - 4:14It's exciting to be able
to make new proteins, -
4:14 - 4:17because despite the diversity in nature,
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4:17 - 4:23evolution has only sampled a tiny fraction
of the total number of proteins possible. -
4:24 - 4:27I told you that nature uses
an alphabet of 20 amino acids, -
4:27 - 4:32and a typical protein is a chain
of about 100 amino acids, -
4:32 - 4:37so the total number of possibilities
is 20 times 20 times 20, 100 times, -
4:37 - 4:41which is a number on the order
of 10 to the 130th power, -
4:41 - 4:45which is enormously more
than the total number of proteins -
4:45 - 4:47which have existed
since life on earth began. -
4:48 - 4:51And it's this unimaginably large space
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4:51 - 4:54we can now explore
using computational protein design. -
4:56 - 4:58Now the proteins that exist on earth
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4:58 - 5:02evolved to solve the problems
faced by natural evolution. -
5:03 - 5:05For example, replicating the genome.
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5:06 - 5:08But we face new challenges today.
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5:08 - 5:11We live longer, so new
diseases are important. -
5:11 - 5:13We're heating up and polluting the planet,
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5:13 - 5:17so we face a whole host
of ecological challenges. -
5:18 - 5:20If we had a million years to wait,
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5:20 - 5:23new proteins might evolve
to solve those challenges. -
5:24 - 5:26But we don't have
millions of years to wait. -
5:26 - 5:29Instead, with computational
protein design, -
5:29 - 5:34we can design new proteins
to address these challenges today. -
5:36 - 5:40Our audacious idea is to bring
biology out of the Stone Age -
5:40 - 5:43through technological revolution
in protein design. -
5:44 - 5:47We've already shown
that we can design new proteins -
5:47 - 5:49with new shapes and functions.
-
5:49 - 5:53For example, vaccines work
by stimulating your immune system -
5:54 - 5:57to make a strong response
against a pathogen. -
5:58 - 5:59To make better vaccines,
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5:59 - 6:02we've designed protein particles
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6:02 - 6:05to which we can fuse
proteins from pathogens, -
6:05 - 6:10like this blue protein here,
from the respiratory virus RSV. -
6:10 - 6:12To make vaccine candidates
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6:12 - 6:16that are literally bristling
with the viral protein, -
6:16 - 6:18we find that such vaccine candidates
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6:18 - 6:21produce a much stronger
immune response to the virus -
6:21 - 6:24than any previous vaccines
that have been tested. -
6:25 - 6:28This is important because RSV
is currently one of the leading causes -
6:29 - 6:31of infant mortality worldwide.
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6:32 - 6:36We've also designed new proteins
to break down gluten in your stomach -
6:36 - 6:38for celiac disease
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6:38 - 6:42and other proteins to stimulate
your immune system to fight cancer. -
6:43 - 6:47These advances are the beginning
of the protein design revolution. -
6:49 - 6:52We've been inspired by a previous
technological revolution: -
6:52 - 6:53the digital revolution,
-
6:53 - 6:59which took place in large part
due to advances in one place, -
6:59 - 7:00Bell Laboratories.
-
7:00 - 7:04Bell Labs was a place with an open,
collaborative environment, -
7:04 - 7:07and was able to attract top talent
from around the world. -
7:07 - 7:11And this led to a remarkable
string of innovations -- -
7:11 - 7:15the transistor, the laser,
satellite communication -
7:15 - 7:17and the foundations of the internet.
-
7:18 - 7:22Our goal is to build
the Bell Laboratories of protein design. -
7:22 - 7:26We are seeking to attract
talented scientists from around the world -
7:26 - 7:29to accelerate the protein
design revolution, -
7:29 - 7:33and we'll be focusing
on five grand challenges. -
7:34 - 7:40First, by taking proteins from flu strains
from around the world -
7:40 - 7:43and putting them on top
of the designed protein particles -
7:43 - 7:45I showed you earlier,
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7:45 - 7:48we aim to make a universal flu vaccine,
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7:48 - 7:52one shot of which gives a lifetime
of protection against the flu. -
7:53 - 7:55The ability to design --
-
7:55 - 8:00(Applause)
-
8:00 - 8:03The ability to design
new vaccines on the computer -
8:03 - 8:09is important both to protect
against natural flu epidemics -
8:09 - 8:12and, in addition, intentional
acts of bioterrorism. -
8:13 - 8:17Second, we're going far beyond
nature's limited alphabet -
8:17 - 8:18of just 20 amino acids
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8:18 - 8:23to design new therapeutic candidates
for conditions such as chronic pain, -
8:23 - 8:26using an alphabet
of thousands of amino acids. -
8:27 - 8:30Third, we're building
advanced delivery vehicles -
8:30 - 8:35to target existing medications
exactly where they need to go in the body. -
8:35 - 8:38For example, chemotherapy to a tumor
-
8:38 - 8:42or gene therapies to the tissue
where gene repair needs to take place. -
8:43 - 8:50Fourth, we're designing smart therapeutics
that can do calculations within the body -
8:50 - 8:52and go far beyond current medicines,
-
8:52 - 8:54which are really blunt instruments.
-
8:54 - 8:58For example, to target a small
subset of immune cells -
8:58 - 9:01responsible for an autoimmune disorder,
-
9:01 - 9:04and distinguish them from the vast
majority of healthy immune cells. -
9:05 - 9:08Finally, inspired by remarkable
biological materials -
9:08 - 9:13such as silk, abalone shell,
tooth and others, -
9:13 - 9:16we're designing new
protein-based materials -
9:16 - 9:21to address challenges in energy
and ecological issues. -
9:22 - 9:24To do all this,
we're growing our institute. -
9:25 - 9:30We seek to attract energetic,
talented and diverse scientists -
9:30 - 9:33from around the world,
at all career stages, -
9:33 - 9:35to join us.
-
9:35 - 9:39You can also participate
in the protein design revolution -
9:39 - 9:42through our online
folding and design game, "Foldit." -
9:43 - 9:47And through our distributed
computing project, Rosetta@home, -
9:47 - 9:51which you can join from your laptop
or your Android smartphone. -
9:53 - 9:57Making the world a better place
through protein design is my life's work. -
9:57 - 9:59I'm so excited about
what we can do together. -
10:00 - 10:01I hope you'll join us,
-
10:01 - 10:02and thank you.
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10:02 - 10:07(Applause and cheers)
- Title:
- 5 challenges we could solve by designing new proteins
- Speaker:
- David Baker
- Description:
-
Proteins are remarkable molecular machines: they digest your food, fire your neurons, power your immune system and so much more. What if we could design new ones, with functions never before seen in nature? In this remarkable glimpse of the future, David Baker shares how his team at the Institute for Protein Design is creating entirely new proteins from scratch -- and shows how they could help us tackle five massive challenges facing humanity. (This ambitious plan is a part of the Audacious Project, TED's initiative to inspire and fund global change.)
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 10:24
Oliver Friedman edited English subtitles for 5 challenges we could solve by designing new proteins | ||
Oliver Friedman edited English subtitles for 5 challenges we could solve by designing new proteins | ||
Oliver Friedman approved English subtitles for 5 challenges we could solve by designing new proteins | ||
Oliver Friedman edited English subtitles for 5 challenges we could solve by designing new proteins | ||
Krystian Aparta accepted English subtitles for 5 challenges we could solve by designing new proteins | ||
Krystian Aparta edited English subtitles for 5 challenges we could solve by designing new proteins | ||
Leslie Gauthier edited English subtitles for 5 challenges we could solve by designing new proteins | ||
Leslie Gauthier edited English subtitles for 5 challenges we could solve by designing new proteins |