[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,I'm going to tell you about the most\Namazing machines in the world ...
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,And what we can now do with them.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Proteins,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,some of which you see inside a cell here,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,carry out essentially all the important\Nfunctions in our bodies.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Proteins digest your food,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,contract your muscles,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,fire your neurons
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and power your immune system.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Everything that happens in biology --
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,almost --
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,happens because of proteins.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Proteins are linear chains\Nof building blocks called amino acids.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Nature uses an alphabet\Nof 20 amino acids,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,some of which have names\Nyou may have heard of.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,In this picture, for scale,\Neach bump is an atom.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Chemical forces between the amino acids\Ncause these long stringy molecules
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to fold up into unique,\Nthree-dimensional structures.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The folding process,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,while it looks random,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,it is in fact very precise.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Each protein folds to its characteristic\Nshape each time,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and the folding process takes just\Na fraction of a second.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,And it's the shapes of proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which enable them to carry out\Ntheir remarkable biological functions.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,For example,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,hemoglobin has a shape\Nin the lungs perfectly suited
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,for binding a molecule of oxygen.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,When hemoglobin moves to your muscle,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,the shape changes slightly
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and the oxygen comes out.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The shapes of proteins,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and hence their remarkable functions,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,are completely specified by the sequence\Nof amino acids in the protein chain.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,In this picture, each letter on top\Nis an amino acide.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Where do these sequences come from?
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The genes in your genome \Nspecify the amino acid sequences
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,of your proteins.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Each gene encodes the amino acid\Nsequence of a single protein.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The translation between these amino\Nacid sequences and the structures
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and funcions of proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,is known as the protein-folding problem.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,It's a very hard problem
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,because there's so many different\Nshape a protein can adopt.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Because of this complexity,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,humans have only been able\Nto harness the power of proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,by making very small changes\Nto the amino acid sequences
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,of the proteins we found in nature.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,This is similar to the process\Nthat our Stone Age ancestors used
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to make tools and other implements\Nfrom the sticks and stones
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,that we found in the world around us.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,But humans did not learn to fly\Nby modifying birds.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Instead, scientists inspired by birds,\Nuncovered the principles of aerodynamics.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Engineers then used those principles\Nto design custom flying machines.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,In a similar way,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we've been working for a number of years
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to uncover the fundamental principles\Nof protein folding
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and encoding those principles\Nin the computer program called "Rosetta."
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We made a breakthrough in recent years.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We can now design completely new proteins\Nfrom scratch on the computer.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Once we've designed the new protein,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we encode its amino acid sequence\Nin a synthetic gene.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We have to make a synthetic gene
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,because since the protein\Nis completely new,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,there's no gene in any organism on earth\Nwhich currently exists that encodes it.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Our advances in understanding\Nprotein folding
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and how to design proteins,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,coupled with the decreasing cost\Nof gene synthesis
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and the More's Law increase\Nin computer power,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,now enable us to design tens\Nof thousands of new proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,with new shapes and new functions\Non the computer,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and encode each one of those\Nin a synthetic gene.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Once we have those synthetic genes,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we put them into bacteria
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to program them to make\Nthese brand new proteins.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We then extract the proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and determine whether they function\Nas we designed them to do
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and whether they're safe.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,It's exciting to be able\Nto make new proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,because despite the diversity in nature,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,evolution has only sampled a tiny fraction\Nof the total number of proteins possible.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,I told you that nature uses\Nan alphabet of 20 amino acids,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and a typical protein is a chain\Nof about 100 amino acids,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,so the total number of possibilities\Nis 20 times 20 times 20, 100 times,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which is a number on the order\Nof 10 to the 130th power,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which is enormously more\Nthan the total number of proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which have existed\Nsince life on earth began.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,And it's this unimaginably large space\Nwe can now explore
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,using computational protein design.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Now the proteins that exist on earth\N
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,evolved to solve the problems\Nfaced by natural evolution.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,For example, replicating the genome.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,But we face new challenges today.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We live longer, so new\Ndiseases are important.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We're heating up and polluting the planet,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,so we face a full host\Nof ecological challenges.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,If we had a million years to wait,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,new proteins might evolve\Nto solve those challenges.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,But we don't have\Nmillions of years to wait.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Instead, with computational\Nprotein design,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we can design new proteins\Nto address these challenges today.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Our audacious idea is to bring\Nbiology out of the Stone Age
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,through technological revolution\Nin protein design.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We've already shown\Nthat we can design new proteins
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,with new shapes and functions.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,For example, vaccines work\Nmy stimulating your immune system
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to make a strong response\Nagainst a pathogen.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,To make better vaccines,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we've designed protein particles
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to which we confuse\Nproteins from pathogens,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,like this blue protein here\Nfrom the respiratory virus RSV.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,To make vaccine candidates
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,that are literally bristling\Nwith the viral protein,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we find that such vaccine candidates
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,produce a much stronger\Nimmune response to the virus
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,than any previous vaccines\Nthat have been tested.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,This is important because RSV\Nis currently one of the leading causes
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,of infant mortality worldwide.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We've also designed new proteins\Nto break down gluten in your stomach
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,for Celiac's Disease,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and other proteins to stimulate\Nyour immune system to fight cancer.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,These advances are the beginning\Nof the protein-design revolution.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We've been inspired by a precious\Ntechnological revolution:
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,the Digital Revolution,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which took place in large part\Ndue to advances in one place --
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Bell Laboratories.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The Labs was a place with an open,\Ncollaborative environment
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and was able to attract top talent\Nfrom around the world.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,And this led to a remarkable\Nstring of innovations --
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,the transistor,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,the laser,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,satellite communication
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and the foundations of the internet.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Our goal is to build\Nthe Bell Laboratories of protein design.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,We are seeking to attract\Ntalented scientists from around the world
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to accelerate the protein\Ndesign revolution,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and we'll be focusing on five\Ngrand challenges.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,First, by taking proteins from flu strains\Nfrom around the world
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and putting them on top\Nof the design protein particles
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,I showed you earlier,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,we aim to make a universal flu vaccine,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,one shot of which gives a lifetime\Nof protection against the flu.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The ability to design --
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,The ability to design\Nnew vaccines on the computer
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,is important both to protecting\Nagainst natural flu epidemics
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and in addition, intentional\Nacts of bioterrorism.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Second, we're going far beyond\Nnature's limited alphabet
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,of just 20 amino acids
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to design new therapeutic candidates\Nfor conditions such a chronic pain,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,using an alphabet\Nof thousands of amino acids.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Third, we're building\Nadvanced delivery vehicles
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,to targe existing medications\Nexactly where they need to go in the body.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,For example, chemotherapy to a tumor
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,or gene therapies to the tissue\Nwhere gene repair needs to take place.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Fourth, we're designing smart therapeutics\Nthat can do calculations within the body
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and go far beyond current medicines,
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,which are really blunt instruments.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,For example, to target a small\Nsubset of immune cells
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,responsible for an autoimmune disorder
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,and distinguish them from the vast\Nmajority of healthy immune cells.
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,Finally, inspired by remarkable\Nbiological materials
Dialogue: 0,9:59:59.99,9:59:59.99,Default,,0000,0000,0000,,such as silk, Abalone shell,