WEBVTT

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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)