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  • I'm going to tell you about the most amazing machines in the world

  • and what we can now do with them.

  • Proteins,

  • some of which you see inside a cell here,

  • carry out essentially all the important functions in our bodies.

  • Proteins digest your food,

  • contract your muscles,

  • fire your neurons

  • and power your immune system.

  • Everything that happens in biology --

  • almost --

  • happens because of proteins.

  • Proteins are linear chains of building blocks called amino acids.

  • Nature uses an alphabet of 20 amino acids,

  • some of which have names you may have heard of.

  • In this picture, for scale, each bump is an atom.

  • Chemical forces between the amino acids cause these long stringy molecules

  • to fold up into unique, three-dimensional structures.

  • The folding process,

  • while it looks random,

  • is in fact very precise.

  • Each protein folds to its characteristic shape each time,

  • and the folding process takes just a fraction of a second.

  • And it's the shapes of proteins

  • which enable them to carry out their remarkable biological functions.

  • For example,

  • hemoglobin has a shape in the lungs perfectly suited

  • for binding a molecule of oxygen.

  • When hemoglobin moves to your muscle,

  • the shape changes slightly

  • and the oxygen comes out.

  • The shapes of proteins,

  • and hence their remarkable functions,

  • are completely specified by the sequence of amino acids in the protein chain.

  • In this picture, each letter on top is an amino acid.

  • Where do these sequences come from?

  • The genes in your genome specify the amino acid sequences

  • of your proteins.

  • Each gene encodes the amino acid sequence of a single protein.

  • The translation between these amino acid sequences

  • and the structures and functions of proteins

  • is known as the protein folding problem.

  • It's a very hard problem

  • because there's so many different shapes a protein can adopt.

  • Because of this complexity,

  • humans have only been able to harness the power of proteins

  • by making very small changes to the amino acid sequences

  • of the proteins we've found in nature.

  • This is similar to the process that our Stone Age ancestors used

  • to make tools and other implements from the sticks and stones

  • that we found in the world around us.

  • But humans did not learn to fly by modifying birds.

  • (Laughter)

  • Instead, scientists, inspired by birds, uncovered the principles of aerodynamics.

  • Engineers then used those principles to design custom flying machines.

  • In a similar way,

  • we've been working for a number of years

  • to uncover the fundamental principles of protein folding

  • and encoding those principles in the computer program called Rosetta.

  • We made a breakthrough in recent years.

  • We can now design completely new proteins from scratch on the computer.

  • Once we've designed the new protein,

  • we encode its amino acid sequence in a synthetic gene.

  • We have to make a synthetic gene

  • because since the protein is completely new,

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

  • Our advances in understanding protein folding

  • and how to design proteins,

  • coupled with the decreasing cost of gene synthesis

  • and the Moore's law increase in computing power,

  • now enable us to design tens of thousands of new proteins,

  • with new shapes and new functions,

  • on the computer,

  • and encode each one of those in a synthetic gene.

  • Once we have those synthetic genes,

  • we put them into bacteria

  • to program them to make these brand-new proteins.

  • We then extract the proteins

  • and determine whether they function as we designed them to

  • and whether they're safe.

  • It's exciting to be able to make new proteins,

  • because despite the diversity in nature,

  • evolution has only sampled a tiny fraction of the total number of proteins possible.

  • I told you that nature uses an alphabet of 20 amino acids,

  • and a typical protein is a chain of about 100 amino acids,

  • so the total number of possibilities is 20 times 20 times 20, 100 times,

  • which is a number on the order of 10 to the 130th power,

  • which is enormously more than the total number of proteins

  • which have existed since life on earth began.

  • And it's this unimaginably large space

  • we can now explore using computational protein design.

  • Now the proteins that exist on earth

  • evolved to solve the problems faced by natural evolution.

  • For example, replicating the genome.

  • But we face new challenges today.

  • We live longer, so new diseases are important.

  • We're heating up and polluting the planet,

  • so we face a whole host of ecological challenges.

  • If we had a million years to wait,

  • new proteins might evolve to solve those challenges.

  • But we don't have millions of years to wait.

  • Instead, with computational protein design,

  • we can design new proteins to address these challenges today.

  • Our audacious idea is to bring biology out of the Stone Age

  • through technological revolution in protein design.

  • We've already shown that we can design new proteins

  • with new shapes and functions.

  • For example, vaccines work by stimulating your immune system

  • to make a strong response against a pathogen.

  • To make better vaccines,

  • we've designed protein particles

  • to which we can fuse proteins from pathogens,

  • like this blue protein here, from the respiratory virus RSV.

  • To make vaccine candidates

  • that are literally bristling with the viral protein,

  • we find that such vaccine candidates

  • produce a much stronger immune response to the virus

  • than any previous vaccines that have been tested.

  • This is important because RSV is currently one of the leading causes

  • of infant mortality worldwide.

  • We've also designed new proteins to break down gluten in your stomach

  • for celiac disease

  • and other proteins to stimulate your immune system to fight cancer.

  • These advances are the beginning of the protein design revolution.

  • We've been inspired by a previous technological revolution:

  • the digital revolution,

  • which took place in large part due to advances in one place,

  • Bell Laboratories.

  • Bell Labs was a place with an open, collaborative environment,

  • and was able to attract top talent from around the world.

  • And this led to a remarkable string of innovations --

  • the transistor, the laser, satellite communication

  • and the foundations of the internet.

  • Our goal is to build the Bell Laboratories of protein design.

  • We are seeking to attract talented scientists from around the world

  • to accelerate the protein design revolution,

  • and we'll be focusing on five grand challenges.

  • First, by taking proteins from flu strains from around the world

  • and putting them on top of the designed protein particles

  • I showed you earlier,

  • we aim to make a universal flu vaccine,

  • one shot of which gives a lifetime of protection against the flu.

  • The ability to design --

  • (Applause)

  • The ability to design new vaccines on the computer

  • is important both to protect against natural flu epidemics

  • and, in addition, intentional acts of bioterrorism.

  • Second, we're going far beyond nature's limited alphabet

  • of just 20 amino acids

  • to design new therapeutic candidates for conditions such as chronic pain,

  • using an alphabet of thousands of amino acids.

  • Third, we're building advanced delivery vehicles

  • to target existing medications exactly where they need to go in the body.

  • For example, chemotherapy to a tumor

  • or gene therapies to the tissue where gene repair needs to take place.

  • Fourth, we're designing smart therapeutics that can do calculations within the body

  • and go far beyond current medicines,

  • which are really blunt instruments.

  • For example, to target a small subset of immune cells

  • responsible for an autoimmune disorder,

  • and distinguish them from the vast majority of healthy immune cells.

  • Finally, inspired by remarkable biological materials

  • such as silk, abalone shell, tooth and others,

  • we're designing new protein-based materials

  • to address challenges in energy and ecological issues.

  • To do all this, we're growing our institute.

  • We seek to attract energetic, talented and diverse scientists

  • from around the world, at all career stages,

  • to join us.

  • You can also participate in the protein design revolution

  • through our online folding and design game, "Foldit."

  • And through our distributed computing project, Rosetta@home,

  • which you can join from your laptop or your Android smartphone.

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

  • I'm so excited about what we can do together.

  • I hope you'll join us,

  • and thank you.

  • (Applause and cheers)

I'm going to tell you about the most amazing machines in the world

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B2 US TED protein amino design gene amino acid

【TED】David Baker: 5 challenges we could solve by designing new proteins (5 challenges we could solve by designing new proteins | David Baker)

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    林宜悉 posted on 2019/07/16
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