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I'm going to tell you about the most
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.
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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.
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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.
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In this picture, for scale,
each bump is an atom.
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Chemical forces between the amino acids
cause these long stringy molecules
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to fold up into unique,
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,
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and the folding process
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.
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For example,
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hemoglobin has a shape
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.
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In this picture, each letter
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
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of your proteins.
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Each gene encodes the amino acid
sequence of a single protein.
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The translation between
these amino acid sequences
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and the structures
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.
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Because of this complexity,
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humans have only been able
to harness the power of proteins
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by making very small changes
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
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to make tools and other implements
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.
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(Laughter)
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Instead, scientists, inspired by birds,
uncovered the principles of aerodynamics.
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Engineers then used those principles
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
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and encoding those principles
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.
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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.
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We have to make a synthetic gene
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because since the protein
is completely new,
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there's no gene in any organism on earth
which currently exists that encodes it.
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Our advances in understanding
protein folding
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and how to design proteins,
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coupled with the decreasing cost
of gene synthesis
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and the Moore's law increase
in computing power,
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now enable us to design
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.
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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.
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We then extract the proteins
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and determine whether they function
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,
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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.
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I told you that nature uses
an alphabet of 20 amino acids,
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and a typical protein is a chain
of about 100 amino acids,
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so the total number of possibilities
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,
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which is enormously more
than the total number of proteins
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which have existed
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.
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Now the proteins that exist on earth
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evolved to solve the problems
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.
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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.
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If we had a million years to wait,
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new proteins might evolve
to solve those challenges.
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But we don't have
millions of years to wait.
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Instead, with computational
protein design,
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we can design new proteins
to address these challenges today.
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Our audacious idea is to bring
biology out of the Stone Age
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through technological revolution
in protein design.
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We've already shown
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
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to make a strong response
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,
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like this blue protein here,
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,
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we find that such vaccine candidates
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produce a much stronger
immune response to the virus
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than any previous vaccines
that have been tested.
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This is important because RSV
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
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for celiac disease
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and other proteins to stimulate
your immune system to fight cancer.
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These advances are the beginning
of the protein design revolution.
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We've been inspired by a previous
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,
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Bell Laboratories.
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Bell Labs was a place with an open,
collaborative environment,
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and was able to attract top talent
from around the world.
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And this led to a remarkable
string of innovations --
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the transistor, the laser,
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.
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We are seeking to attract
talented scientists from around the world
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to accelerate the protein
design revolution,
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and we'll be focusing
on five grand challenges.
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First, by taking proteins from flu strains
from around the world
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and putting them on top
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.
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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
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is important both to protect
against natural flu epidemics
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and, in addition, intentional
acts of bioterrorism.
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Second, we're going far beyond
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,
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using an alphabet
of thousands of amino acids.
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Third, we're building
advanced delivery vehicles
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to target existing medications
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.
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Fourth, we're designing smart therapeutics
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
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responsible for an autoimmune disorder,
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and distinguish them from the vast
majority of healthy immune cells.
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Finally, inspired by remarkable
biological materials
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such as silk, abalone shell,
tooth and others,
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we're designing new
protein-based materials
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to address challenges in energy
and ecological issues.
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To do all this,
we're growing our institute.
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We seek to attract energetic,
talented and diverse scientists
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from around the world,
at all career stages,
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to join us.
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You can also participate
in the protein design revolution
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through our online
folding and design game, "Foldit."
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And through our distributed
computing project, Rosetta@home,
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which you can join from your laptop
or your Android smartphone.
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Making the world a better place
through protein design is my life's work.
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I'm so excited about
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)