TED2019
David Baker: 5 challenges we could solve by designing new proteins
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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.)
David Baker - Computational biologist
David Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology. Full bio
David Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology. Full bio
Double-click the English transcript below to play the video.
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I'm going to tell you about the most
amazing machines in the world
amazing machines in the world
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and what we can now do with them.
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Proteins,
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some of which you see inside a cell here,
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carry out essentially all the important
functions in our bodies.
functions in our bodies.
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Proteins digest your food,
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contract your muscles,
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fire your neurons
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and power your immune system.
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Everything that happens in biology --
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almost --
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happens because of proteins.
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Proteins are linear chains
of building blocks called amino acids.
of building blocks called amino acids.
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Nature uses an alphabet of 20 amino acids,
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some of which have names
you may have heard of.
you may have heard of.
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In this picture, for scale,
each bump is an atom.
each bump is an atom.
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Chemical forces between the amino acids
cause these long stringy molecules
cause these long stringy molecules
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to fold up into unique,
three-dimensional structures.
three-dimensional structures.
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The folding process,
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while it looks random,
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is in fact very precise.
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Each protein folds
to its characteristic shape each time,
to its characteristic shape each time,
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and the folding process
takes just a fraction of a second.
takes just a fraction of a second.
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And it's the shapes of proteins
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which enable them to carry out
their remarkable biological functions.
their remarkable biological functions.
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For example,
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hemoglobin has a shape
in the lungs perfectly suited
in the lungs perfectly suited
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for binding a molecule of oxygen.
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When hemoglobin moves to your muscle,
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the shape changes slightly
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and the oxygen comes out.
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The shapes of proteins,
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and hence their remarkable functions,
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are completely specified by the sequence
of amino acids in the protein chain.
of amino acids in the protein chain.
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In this picture, each letter
on top is an amino acid.
on top is an amino acid.
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Where do these sequences come from?
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The genes in your genome
specify the amino acid sequences
specify the amino acid sequences
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of your proteins.
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Each gene encodes the amino acid
sequence of a single protein.
sequence of a single protein.
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The translation between
these amino acid sequences
these amino acid sequences
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and the structures
and functions of proteins
and functions of proteins
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is known as the protein folding problem.
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It's a very hard problem
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because there's so many different
shapes a protein can adopt.
shapes a protein can adopt.
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Because of this complexity,
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humans have only been able
to harness the power of proteins
to harness the power of proteins
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by making very small changes
to the amino acid sequences
to the amino acid sequences
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of the proteins we've found in nature.
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This is similar to the process
that our Stone Age ancestors used
that our Stone Age ancestors used
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to make tools and other implements
from the sticks and stones
from the sticks and stones
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that we found in the world around us.
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But humans did not learn to fly
by modifying birds.
by modifying birds.
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(Laughter)
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Instead, scientists, inspired by birds,
uncovered the principles of aerodynamics.
uncovered the principles of aerodynamics.
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Engineers then used those principles
to design custom flying machines.
to design custom flying machines.
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In a similar way,
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we've been working for a number of years
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to uncover the fundamental
principles of protein folding
principles of protein folding
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and encoding those principles
in the computer program called Rosetta.
in the computer program called Rosetta.
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We made a breakthrough in recent years.
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We can now design completely new proteins
from scratch on the computer.
from scratch on the computer.
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Once we've designed the new protein,
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we encode its amino acid sequence
in a synthetic gene.
in a synthetic gene.
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We have to make a synthetic gene
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because since the protein
is completely new,
is completely new,
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there's no gene in any organism on earth
which currently exists that encodes it.
which currently exists that encodes it.
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Our advances in understanding
protein folding
protein folding
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and how to design proteins,
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coupled with the decreasing cost
of gene synthesis
of gene synthesis
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and the Moore's law increase
in computing power,
in computing power,
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now enable us to design
tens of thousands of new proteins,
tens of thousands of new proteins,
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with new shapes and new functions,
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on the computer,
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and encode each one of those
in a synthetic gene.
in a synthetic gene.
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Once we have those synthetic genes,
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we put them into bacteria
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to program them to make
these brand-new proteins.
these brand-new proteins.
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We then extract the proteins
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and determine whether they function
as we designed them to
as we designed them to
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and whether they're safe.
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It's exciting to be able
to make new proteins,
to make new proteins,
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because despite the diversity in nature,
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evolution has only sampled a tiny fraction
of the total number of proteins possible.
of the total number of proteins possible.
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I told you that nature uses
an alphabet of 20 amino acids,
an alphabet of 20 amino acids,
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and a typical protein is a chain
of about 100 amino acids,
of about 100 amino acids,
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so the total number of possibilities
is 20 times 20 times 20, 100 times,
is 20 times 20 times 20, 100 times,
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which is a number on the order
of 10 to the 130th power,
of 10 to the 130th power,
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which is enormously more
than the total number of proteins
than the total number of proteins
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which have existed
since life on earth began.
since life on earth began.
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And it's this unimaginably large space
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we can now explore
using computational protein design.
using computational protein design.
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Now the proteins that exist on earth
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evolved to solve the problems
faced by natural evolution.
faced by natural evolution.
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For example, replicating the genome.
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But we face new challenges today.
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We live longer, so new
diseases are important.
diseases are important.
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We're heating up and polluting the planet,
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so we face a whole host
of ecological challenges.
of ecological challenges.
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If we had a million years to wait,
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new proteins might evolve
to solve those challenges.
to solve those challenges.
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But we don't have
millions of years to wait.
millions of years to wait.
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Instead, with computational
protein design,
protein design,
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we can design new proteins
to address these challenges today.
to address these challenges today.
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Our audacious idea is to bring
biology out of the Stone Age
biology out of the Stone Age
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through technological revolution
in protein design.
in protein design.
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We've already shown
that we can design new proteins
that we can design new proteins
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with new shapes and functions.
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For example, vaccines work
by stimulating your immune system
by stimulating your immune system
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to make a strong response
against a pathogen.
against a pathogen.
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To make better vaccines,
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we've designed protein particles
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to which we can fuse
proteins from pathogens,
proteins from pathogens,
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like this blue protein here,
from the respiratory virus RSV.
from the respiratory virus RSV.
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To make vaccine candidates
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that are literally bristling
with the viral protein,
with the viral protein,
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we find that such vaccine candidates
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produce a much stronger
immune response to the virus
immune response to the virus
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than any previous vaccines
that have been tested.
that have been tested.
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This is important because RSV
is currently one of the leading causes
is currently one of the leading causes
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of infant mortality worldwide.
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We've also designed new proteins
to break down gluten in your stomach
to break down gluten in your stomach
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for celiac disease
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and other proteins to stimulate
your immune system to fight cancer.
your immune system to fight cancer.
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These advances are the beginning
of the protein design revolution.
of the protein design revolution.
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We've been inspired by a previous
technological revolution:
technological revolution:
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the digital revolution,
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which took place in large part
due to advances in one place,
due to advances in one place,
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Bell Laboratories.
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Bell Labs was a place with an open,
collaborative environment,
collaborative environment,
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and was able to attract top talent
from around the world.
from around the world.
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And this led to a remarkable
string of innovations --
string of innovations --
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the transistor, the laser,
satellite communication
satellite communication
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and the foundations of the internet.
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Our goal is to build
the Bell Laboratories of protein design.
the Bell Laboratories of protein design.
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We are seeking to attract
talented scientists from around the world
talented scientists from around the world
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to accelerate the protein
design revolution,
design revolution,
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and we'll be focusing
on five grand challenges.
on five grand challenges.
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First, by taking proteins from flu strains
from around the world
from around the world
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and putting them on top
of the designed protein particles
of the designed protein particles
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I showed you earlier,
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we aim to make a universal flu vaccine,
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one shot of which gives a lifetime
of protection against the flu.
of protection against the flu.
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The ability to design --
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(Applause)
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The ability to design
new vaccines on the computer
new vaccines on the computer
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is important both to protect
against natural flu epidemics
against natural flu epidemics
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and, in addition, intentional
acts of bioterrorism.
acts of bioterrorism.
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Second, we're going far beyond
nature's limited alphabet
nature's limited alphabet
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of just 20 amino acids
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to design new therapeutic candidates
for conditions such as chronic pain,
for conditions such as chronic pain,
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using an alphabet
of thousands of amino acids.
of thousands of amino acids.
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Third, we're building
advanced delivery vehicles
advanced delivery vehicles
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to target existing medications
exactly where they need to go in the body.
exactly where they need to go in the body.
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For example, chemotherapy to a tumor
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or gene therapies to the tissue
where gene repair needs to take place.
where gene repair needs to take place.
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Fourth, we're designing smart therapeutics
that can do calculations within the body
that can do calculations within the body
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and go far beyond current medicines,
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which are really blunt instruments.
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For example, to target a small
subset of immune cells
subset of immune cells
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responsible for an autoimmune disorder,
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and distinguish them from the vast
majority of healthy immune cells.
majority of healthy immune cells.
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Finally, inspired by remarkable
biological materials
biological materials
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such as silk, abalone shell,
tooth and others,
tooth and others,
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we're designing new
protein-based materials
protein-based materials
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to address challenges in energy
and ecological issues.
and ecological issues.
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To do all this,
we're growing our institute.
we're growing our institute.
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We seek to attract energetic,
talented and diverse scientists
talented and diverse scientists
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from around the world,
at all career stages,
at all career stages,
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to join us.
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You can also participate
in the protein design revolution
in the protein design revolution
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through our online
folding and design game, "Foldit."
folding and design game, "Foldit."
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And through our distributed
computing project, Rosetta@home,
computing project, Rosetta@home,
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which you can join from your laptop
or your Android smartphone.
or your Android smartphone.
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Making the world a better place
through protein design is my life's work.
through protein design is my life's work.
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I'm so excited about
what we can do together.
what we can do together.
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I hope you'll join us,
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and thank you.
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(Applause and cheers)
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ABOUT THE SPEAKER
David Baker - Computational biologistDavid Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology.
Why you should listen
David Baker is fascinated by biological self-organization. For example: How does the information stored in DNA translate into the intricate world of proteins and cells? The DNA code was solved more than 50 years ago, but the protein folding code has remained one of biology's greatest challenges. Starting 20 years ago, Baker's research team began using computers to model the structures of proteins. His work has advanced to the point where he can now not only predict the shape of natural proteins but also design completely new ones. In recent years, he's designed new experimental cancer therapies, vaccines, nanomaterials and more. He believes that the emerging field of protein design will fundamentally change how people make medicines, materials and more around the world. Now that the protein folding code is solved, the sky's the limit.
Baker is a Professor of Biochemistry and the Director of the Institute for Protein Design at the University of Washington in Seattle. He's also an Investigator at the Howard Hughes Medical Institute and Adjunct Professor of Genome Sciences, Bioengineering, Chemical Engineering, Computer Science, and Physics at the UW. With his colleagues, he developed the Rosetta Commons, the Rosetta@Home project and Foldit, a science video game. He has also launched more than ten companies that are seeking to bring designed proteins into the real world.
David Baker | Speaker | TED.com