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I'm going to tell you about the most[br]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[br]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[br]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[br]you may have heard of.

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In this picture, for scale,[br]each bump is an atom.

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Chemical forces between the amino acids[br]cause these long stringy molecules

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to fold up into unique,[br]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[br]to its characteristic shape each time,

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and the folding process[br]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[br]their remarkable biological functions.

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For example,

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hemoglobin has a shape[br]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[br]of amino acids in the protein chain.

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In this picture, each letter[br]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[br]specify the amino acid sequences

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of your proteins.

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Each gene encodes the amino acid[br]sequence of a single protein.

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The translation between[br]these amino acid sequences

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and the structures[br]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[br]shapes a protein can adopt.

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Because of this complexity,

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humans have only been able[br]to harness the power of proteins

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by making very small changes[br]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[br]that our Stone Age ancestors used

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to make tools and other implements[br]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[br]by modifying birds.

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(Laughter)

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Instead, scientists, inspired by birds,[br]uncovered the principles of aerodynamics.

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Engineers then used those principles[br]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[br]principles of protein folding

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and encoding those principles[br]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[br]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[br]in a synthetic gene.

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We have to make a synthetic gene

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because since the protein[br]is completely new,

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there's no gene in any organism on earth[br]which currently exists that encodes it.

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Our advances in understanding[br]protein folding

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and how to design proteins,

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coupled with the decreasing cost[br]of gene synthesis

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and the Moore's law increase[br]in computing power,

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now enable us to design[br]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[br]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[br]these brand-new proteins.

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We then extract the proteins

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and determine whether they function[br]as we designed them to

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and whether they're safe.

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It's exciting to be able[br]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[br]of the total number of proteins possible.

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I told you that nature uses[br]an alphabet of 20 amino acids,

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and a typical protein is a chain[br]of about 100 amino acids,

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so the total number of possibilities[br]is 20 times 20 times 20, 100 times,

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which is a number on the order[br]of 10 to the 130th power,

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which is enormously more[br]than the total number of proteins

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which have existed[br]since life on earth began.

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And it's this unimaginably large space

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we can now explore[br]using computational protein design.

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Now the proteins that exist on earth

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evolved to solve the problems[br]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[br]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[br]of ecological challenges.

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If we had a million years to wait,

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new proteins might evolve[br]to solve those challenges.

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But we don't have[br]millions of years to wait.

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Instead, with computational[br]protein design,

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we can design new proteins[br]to address these challenges today.

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Our audacious idea is to bring[br]biology out of the Stone Age

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through technological revolution[br]in protein design.

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We've already shown[br]that we can design new proteins

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with new shapes and functions.

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For example, vaccines work[br]by stimulating your immune system

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to make a strong response[br]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[br]proteins from pathogens,

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like this blue protein here,[br]from the respiratory virus RSV.

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To make vaccine candidates

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that are literally bristling[br]with the viral protein,

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we find that such vaccine candidates

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produce a much stronger[br]immune response to the virus

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than any previous vaccines[br]that have been tested.

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This is important because RSV[br]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[br]to break down gluten in your stomach

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for celiac disease

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and other proteins to stimulate[br]your immune system to fight cancer.

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These advances are the beginning[br]of the protein design revolution.

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We've been inspired by a previous[br]technological revolution:

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the digital revolution,

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which took place in large part[br]due to advances in one place,

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Bell Laboratories.

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Bell Labs was a place with an open,[br]collaborative environment,

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and was able to attract top talent[br]from around the world.

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And this led to a remarkable[br]string of innovations --

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the transistor, the laser,[br]satellite communication

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and the foundations of the internet.

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Our goal is to build[br]the Bell Laboratories of protein design.

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We are seeking to attract[br]talented scientists from around the world

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to accelerate the protein[br]design revolution,

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and we'll be focusing[br]on five grand challenges.

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First, by taking proteins from flu strains[br]from around the world

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and putting them on top[br]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[br]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[br]new vaccines on the computer

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is important both to protect[br]against natural flu epidemics

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and, in addition, intentional[br]acts of bioterrorism.

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Second, we're going far beyond[br]nature's limited alphabet

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of just 20 amino acids

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to design new therapeutic candidates[br]for conditions such as chronic pain,

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using an alphabet[br]of thousands of amino acids.

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Third, we're building[br]advanced delivery vehicles

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to target existing medications[br]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[br]where gene repair needs to take place.

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Fourth, we're designing smart therapeutics[br]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[br]subset of immune cells

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responsible for an autoimmune disorder,

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and distinguish them from the vast[br]majority of healthy immune cells.

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Finally, inspired by remarkable[br]biological materials

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such as silk, abalone shell,[br]tooth and others,

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we're designing new[br]protein-based materials

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to address challenges in energy[br]and ecological issues.

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To do all this,[br]we're growing our institute.

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We seek to attract energetic,[br]talented and diverse scientists

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from around the world,[br]at all career stages,

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to join us.

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You can also participate[br]in the protein design revolution

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through our online[br]folding and design game, "Foldit."

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And through our distributed[br]computing project, Rosetta@home,

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which you can join from your laptop[br]or your Android smartphone.

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Making the world a better place[br]through protein design is my life's work.

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I'm so excited about[br]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)