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

    譯者: Helen Chang 審譯者: Bruce Sung

  • and what we can now do with them.

    我將講述世界上最神奇的機器

  • Proteins,

    以及我們現在能用它來做什麼。

  • some of which you see inside a cell here,

    你在細胞中看到的一些蛋白質,

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

    基本上在我們體內 執行所有重要的功能。

  • Proteins digest your food,

    蛋白質可消化食物、

  • contract your muscles,

    收縮肌肉、

  • fire your neurons

    激發神經元,

  • and power your immune system.

    為免疫系統提供動力。

  • Everything that happens in biology --

    生物學中發生的一切,

  • almost --

    幾乎全都因蛋白質而發生。

  • happens because of proteins.

    蛋白質是由稱為「氨基酸」的 積木構成的線性鏈。

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

    大自然用了 20 種氨基酸字母,

  • Nature uses an alphabet of 20 amino acids,

    你們可能聽過其中若干名稱。

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

    這圖中比例相對的 每個凹凸都是個原子。

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

    氨基酸間的化學力 使這些長而細的分子

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

    折疊成獨特的立體結構。

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

    雖然折疊的過程看似隨機,

  • The folding process,

    實際上非常的精確。

  • while it looks random,

    蛋白質總是折疊成其特徵的形狀,

  • is in fact very precise.

    而折疊的過程只需幾分之一秒。

  • Each protein folds to its characteristic shape each time,

    蛋白質的形狀

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

    使其能夠發揮卓越的生物功能。

  • And it's the shapes of proteins

    例如,

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

    肺裡的血紅蛋白

  • For example,

    具有完全適合結合氧分子的形狀。

  • hemoglobin has a shape in the lungs perfectly suited

    當血紅蛋白移到肌肉時,

  • for binding a molecule of oxygen.

    形狀會稍微改變,

  • When hemoglobin moves to your muscle,

    釋出氧氣。

  • the shape changes slightly

    蛋白質的形狀及其奇妙的功能

  • and the oxygen comes out.

    完全由蛋白質鏈的氨基酸序列所定。

  • The shapes of proteins,

    這張圖片頂部的每個字母都是氨基酸。

  • and hence their remarkable functions,

    這些序列來自哪裡?

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

    基因組中的基因

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

    訂定蛋白質的氨基酸序列。

  • Where do these sequences come from?

    每個基因

  • The genes in your genome specify the amino acid sequences

    為單個蛋白質的氨基酸序列編碼。

  • of your proteins.

    這些氨基酸序列

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

    與蛋白質的結構和功能之間的翻譯

  • The translation between these amino acid sequences

    被稱為蛋白質的折疊問題。

  • and the structures and functions of proteins

    這是個非常困難的問題,

  • is known as the protein folding problem.

    因為蛋白質能有許多不同的形狀。

  • It's a very hard problem

    由於它這麼複雜,

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

    人類只能透由稍微更動

  • Because of this complexity,

    自然界蛋白質的氨基酸序列

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

    來利用蛋白質的能量。

  • by making very small changes to the amino acid sequences

    這相當於石器時代祖先用來製作

  • of the proteins we've found in nature.

    我們在周遭世界發現的

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

    木棒、石製工具和其他工具的過程。

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

    但是人類並非透由 修改鳥類來學習飛行。

  • that we found in the world around us.

    (笑聲)

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

    相反地,受鳥類啟發的科學家 發現氣體動力學的原理,

  • (Laughter)

    接著工程師用這些原理 來設計和製作飛行機器。

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

    多年來,我們已經用類似的方式

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

    揭示蛋白質折疊的基本原理,

  • In a similar way,

    並用名為 Rosetta 的 電腦軟體將這些原理編碼。

  • we've been working for a number of years

    我們近年來有了突破,

  • to uncover the fundamental principles of protein folding

    能夠在電腦上從頭開始 設計全新的蛋白質。

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

    一旦設計出新的蛋白質,

  • We made a breakthrough in recent years.

    我們就會在合成基因中 將其氨基酸序列編碼。

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

    我們必須合成基因

  • Once we've designed the new protein,

    是因為蛋白質是全新的,

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

    目前地球上沒有任何生物體 有它的基因編碼。

  • We have to make a synthetic gene

    我們在理解蛋白質的折疊

  • because since the protein is completely new,

    和如何設計蛋白質方面取得的進展,

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

    加上基因合成費用的降低,

  • Our advances in understanding protein folding

    以及符合摩爾定律提高的運算能力,

  • and how to design proteins,

    使我們現在能夠設計出成千上萬種

  • coupled with the decreasing cost of gene synthesis

    具有新形狀和新功能的新蛋白質,

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

    在電腦上設計,

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

    並編碼合成每個基因。

  • with new shapes and new functions,

    一旦擁有這些合成的基因,

  • on the computer,

    我們將其置入細菌,

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

    讓它們製造這些全新的蛋白質。

  • Once we have those synthetic genes,

    然後我們提取蛋白質,

  • we put them into bacteria

    看它們的功能是否符合我們的設計,

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

    以及它們是否安全。

  • We then extract the proteins

    能製造新的蛋白質令人振奮,

  • and determine whether they function as we designed them to

    因為儘管自然界多姿多樣,

  • and whether they're safe.

    卻只演化出

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

    所有可能的蛋白質 總數中的一小部分。

  • because despite the diversity in nature,

    我說過大自然用了 20 個氨基酸字母,

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

    典型的蛋白質是 大約 100 個氨基酸的長鏈,

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

    所以可能性的總數

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

    是 20 乘以 20 乘以 20,

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

    乘 100 次,

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

    是 10 的 130 次方,

  • which is enormously more than the total number of proteins

    遠遠超過自地球出現生命以來

  • which have existed since life on earth began.

    曾經存在過的蛋白質總數。

  • And it's this unimaginably large space

    而這正是我們現在能用運算能力 來設計和探索蛋白質的

  • we can now explore using computational protein design.

    難以想像的廣大空間。

  • Now the proteins that exist on earth

    現存地球的蛋白質以進化

  • evolved to solve the problems faced by natural evolution.

    來解決自然演化所面臨的問題。

  • For example, replicating the genome.

    例如,複製基因組。

  • But we face new challenges today.

    但我們今天面臨新的挑戰。

  • We live longer, so new diseases are important.

    我們活得更長, 因此新疾病極其重要。

  • We're heating up and polluting the planet,

    我們正污染地球和令其升溫,

  • so we face a whole host of ecological challenges.

    因此面臨著一系列的生態挑戰。

  • If we had a million years to wait,

    如果我們能等百萬年,

  • new proteins might evolve to solve those challenges.

    新的蛋白質演化 或許能解決這些挑戰。

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

    但我們無法等上百萬年。

  • Instead, with computational protein design,

    取而代之,透由運算來設計蛋白質,

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

    我們能設計新的蛋白質 來對付當前的挑戰。

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

    我們的大膽想法

  • through technological revolution in protein design.

    是透由蛋白質設計的技術革命

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

    帶生物學跳脫石器時代。

  • with new shapes and functions.

    我們已經證明能夠設計出

  • For example, vaccines work by stimulating your immune system

    具有新形狀、新功能的新蛋白質。

  • to make a strong response against a pathogen.

    例如,疫苗透由刺激免疫系統

  • To make better vaccines,

    對病原體產生強烈的反應作用。

  • we've designed protein particles

    為了製造更好的疫苗,

  • to which we can fuse proteins from pathogens,

    我們設計蛋白質顆粒

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

    來融合病原體中的蛋白質——

  • To make vaccine candidates

    就像此處藍色的蛋白質,

  • that are literally bristling with the viral protein,

    取自呼吸道融合病毒 RSV。 (Respiratory Syncytial Virus)

  • we find that such vaccine candidates

    為確認候選的疫苗 真的含有病毒蛋白,

  • produce a much stronger immune response to the virus

    我們發現這候選疫苗 對病毒的免疫反應

  • than any previous vaccines that have been tested.

    勝過先前已經測試過的任何疫苗。

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

    這很重要,因為 呼吸道融合病毒 RSV

  • of infant mortality worldwide.

    目前是全球嬰兒夭折的主要原因之一。

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

    我們還設計新的蛋白質 來分解胃中的麩質,

  • for celiac disease

    對付腹腔疾病;

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

    也設計其他的蛋白質 來刺激免疫系統對抗癌症。

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

    這些進步是蛋白質設計革命的開始。

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

    我們受先前技術革命的啟發。

  • the digital revolution,

    數位革命大大歸功於

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

    貝爾實驗室所取得的進步。

  • Bell Laboratories.

    貝爾實驗室是個開放、協作的環境,

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

    吸引世界各地的頂尖人才。

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

    這引領一系列的創新:

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

    電晶體、雷射、衛星通信

  • the transistor, the laser, satellite communication

    和網際網路的基礎。

  • and the foundations of the internet.

    我們的目標是建立 蛋白質設計的貝爾實驗室。

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

    我們正尋求吸引 世界各地的優秀科學家

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

    來一起加速蛋白質設計的革命,

  • to accelerate the protein design revolution,

    我們將專注於五大挑戰。

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

    首先經由從世界各地的流感病毒株中

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

    提取蛋白質,

  • and putting them on top of the designed protein particles

    並將它們放在我之前展示的 蛋白質設計顆粒的頂部,

  • I showed you earlier,

    我們著眼於製造 一種通用的流感疫苗,

  • we aim to make a universal flu vaccine,

    打一針就能保護終生免於流感。

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

    設計能力——

  • The ability to design --

    (掌聲)

  • (Applause)

    在電腦上設計新疫苗的能力

  • The ability to design new vaccines on the computer

    對於防止自然的流感疫情

  • is important both to protect against natural flu epidemics

    和防範刻意的生物恐攻都很重要。

  • and, in addition, intentional acts of bioterrorism.

    其次,我們用遠遠超出大自然

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

    有限的 20 個氨基酸字母

  • of just 20 amino acids

    來設計新的治療候選藥物,

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

    來對付像是慢性疼痛,

  • using an alphabet of thousands of amino acids.

    用的是數千種氨基酸字母。

  • Third, we're building advanced delivery vehicles

    第三,我們正在建立先進的載運工具,

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

    以便將現有的藥物準確定位在 它們應該進入的體內位置。

  • For example, chemotherapy to a tumor

    例如,腫瘤的化療,

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

    或修復組織的基因治療。

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

    第四,我們正在設計 能在體內運算的智慧療法,

  • and go far beyond current medicines,

    遠遠超出目前的藥物,

  • which are really blunt instruments.

    那些是非常遲鈍的藥物。

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

    例如,目標對準

  • responsible for an autoimmune disorder,

    造成自身免疫疾病的 一小部分免疫細胞,

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

    將其與絕大多數 健康的免疫細胞區隔開來。

  • Finally, inspired by remarkable biological materials

    最後,靈感來自

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

    絲綢、鮑魚殼、牙齒等 非凡的生物材料,

  • we're designing new protein-based materials

    以及其他材料,

  • to address challenges in energy and ecological issues.

    我們正在設計新的蛋白質基底材料,

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

    以對付能源和生態問題的挑戰。

  • We seek to attract energetic, talented and diverse scientists

    為要做到這一切, 我們正在擴展我們機構。

  • from around the world, at all career stages,

    我們尋求吸引世界各地

  • to join us.

    精力充沛、才華橫溢、 多元的科學家——

  • You can also participate in the protein design revolution

    涵蓋所有的職涯階段——

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

    來加入我們。

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

    你還可以透由我們線上的 折疊和設計遊戲「Foldit」

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

    參與蛋白質設計革命。

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

    透由我們的分散式運算專案 [email protected]

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

    可以在筆記型電腦 或安卓智慧手機上操作。

  • I hope you'll join us,

    透由設計蛋白質使世界變得更好 是我的終生職志。

  • and thank you.

    我們能一起做點什麼的想法 深深鼓舞著我。

  • (Applause and cheers)

    希望你能加入我們。

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

譯者: Helen Chang 審譯者: Bruce Sung

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B2 中高級 中文 美國腔 TED 蛋白質 氨基酸 設計 折疊 基因

【TED】大衛-貝克。我們可以通過設計新的蛋白質來解決的5個挑戰(我們可以通過設計新的蛋白質來解決的5個挑戰|David Baker)。 (【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 發佈於 2021 年 01 月 14 日
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