5 challenges we could solve by designing new proteins | David Baker

翻译人员: Yanyan Hong 校对人员: Cissy Yun

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

我想要向你们分享的是 世界上最惊奇的机理，

and what we can now do with them.

以及我们现在能用它们做些什么。

Proteins,

蛋白质，

some of which you see inside a cell here,

你能在这个细胞中见到它，

carry out essentially all the important functions in our bodies.

基本上负责运行我们 身体中所有重要的功能。

Proteins digest your food,

蛋白质能帮助你消化食物，

contract your muscles,

收缩你的肌肉，

fire your neurons

激发你的神经元，

and power your immune system.

以及为你的免疫系统提供能量。

Everything that happens in biology --

在生物学上，发生的一切——

almost --

几乎一切——

happens because of proteins.

归功于蛋白质。

Proteins are linear chains of building blocks called amino acids.

蛋白质是线性链， 其组件就是氨基酸。

Nature uses an alphabet of 20 amino acids,

大自然使用了 20 个 氨基酸组成的字母表，

some of which have names you may have heard of.

其中的一些名称你或许听说过。

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

在这张图片中，按比例， 每个凸起都是一个原子。

Chemical forces between the amino acids cause these long stringy molecules

氨基酸之间的化学作用力 会导致这些长而细的分子

to fold up into unique, three-dimensional structures.

折叠成独一无二的三维结构。

The folding process,

折叠变化的过程，

while it looks random,

虽然看似随机，

is in fact very precise.

但实际上非常精确。

Each protein folds to its characteristic shape each time,

每个蛋白质每次都会 折叠成它的特有形状，

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

以及整个折叠的过程仅一秒都不到。

And it's the shapes of proteins

而蛋白质的形状

which enable them to carry out their remarkable biological functions.

使它们能够产生非凡的生物功能。

For example,

例如，

hemoglobin has a shape in the lungs perfectly suited

血红蛋白在肺部的形状非常适合

for binding a molecule of oxygen.

用于结合氧分子。

When hemoglobin moves to your muscle,

当血红蛋白进入你的肌肉时，

the shape changes slightly

形状会略有改变，

and the oxygen comes out.

氧气随之释放。

The shapes of proteins,

蛋白质的形状，

and hence their remarkable functions,

以及由此产生的非凡功能，

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

完全由蛋白质链中的氨基酸序列决定。

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

在这张图片中，上面的每个字母 都代表着一种氨基酸。

Where do these sequences come from?

这些序列又是从哪里来的呢？

The genes in your genome specify the amino acid sequences

你基因组中的基因决定了

你的蛋白质分子的氨基酸序列。

of your proteins.

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

每个基因编码形成 一个蛋白质的氨基酸序列。

The translation between these amino acid sequences

这些氨基酸序列

and the structures and functions of proteins

和结构之间的转换 以及蛋白质的功能

is known as the protein folding problem.

被称为蛋白质分子折叠问题。

It's a very hard problem

这是一个非常复杂的问题，

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

因为一个蛋白质分子有太多 不同的形状可以采用。

Because of this complexity,

因为其复杂性，

humans have only been able to harness the power of proteins

人类只能通过对我们在自然界中发现的

by making very small changes to the amino acid sequences

蛋白质的氨基酸序列

of the proteins we've found in nature.

进行微小调整来利用蛋白质的力量。

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

这类似于我们石器时代的祖先

用我们在周围世界发现的

to make tools and other implements from the sticks and stones

木棍和石头制造工具 和其他器械的过程。

that we found in the world around us.

But humans did not learn to fly by modifying birds.

但人类从未通过改造鸟类 来学习飞行。

(Laughter)

（笑声）

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

相反，科学家们受鸟类启发 揭示了空气动力学的原理。

Engineers then used those principles to design custom flying machines.

然后，工程师们利用这些原理 来设计定制的飞行器。

In a similar way,

以同样的方式，

we've been working for a number of years

通过多年的研究，

to uncover the fundamental principles of protein folding

我们已经揭示蛋白质折叠的基本原理，

and encoding those principles in the computer program called Rosetta.

把这些原理编码在一个叫 Rosetta 的计算机程序中。

We made a breakthrough in recent years.

近年来，我们取得了突破，

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

我们现在可以在电脑上， 从头开始设计全新的蛋白质。

Once we've designed the new protein,

一旦我们设计出新型的蛋白质，

we encode its amino acid sequence in a synthetic gene.

我们把它的氨基酸序列 编码在一个合成基因中。

We have to make a synthetic gene

我们必须合成基因，

because since the protein is completely new,

因为蛋白质是全新的，

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

地球上任何现存的生物中 都不存在能够编码它的基因。

Our advances in understanding protein folding

蛋白质折叠的研究进展

and how to design proteins,

以及如何设计新型蛋白质，

coupled with the decreasing cost of gene synthesis

再加上基因合成成本的降低，

and the Moore's law increase in computing power,

和摩尔定律提高了的计算机能力，

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

这些都让我们现在能够 设计数万种新型蛋白质，

with new shapes and new functions,

它们有着新的形状， 以及新的功能，

on the computer,

在电脑上，

and encode each one of those in a synthetic gene.

并编码合成基因中的每一个分子。

Once we have those synthetic genes,

一旦我们有了这些合成基因，

we put them into bacteria

我们把它们放进细菌中，

to program them to make these brand-new proteins.

让它们制造出全新的蛋白质。

We then extract the proteins

然后我们提取这些蛋白质，

and determine whether they function as we designed them to

并确定它们是否就像 我们设想的那样起作用，

and whether they're safe.

以及它们是否安全。

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

能制造出新型蛋白质 真的很令人激动，

because despite the diversity in nature,

因为尽管大自然极具多样性，

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

自然界的进化过程只产生了可能 生成蛋白质总量的一小部分。

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

之前提到，大自然使用 20 个 氨基酸组成的字母表，

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

一个标准的蛋白质是 由 100 个氨基酸组成的链，

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

所以总的可能性是 20 x 20 x 20，这样重复一百次，

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

这是一个 10 的 130 次方的数字，

which is enormously more than the total number of proteins

这远远超过了地球生命伊始时

which have existed since life on earth began.

存在的蛋白质的总数。

And it's this unimaginably large space

而且它是一个难以想象的大空间，

we can now explore using computational protein design.

我们现在可以通过计算机 蛋白质设计进行探索。

Now the proteins that exist on earth

现在地球上存在的蛋白质

evolved to solve the problems faced by natural evolution.

自行进化来面对 大自然进化所产生的问题。

For example, replicating the genome.

例如，再生基因组。

But we face new challenges today.

但现今我们面临着各种新的挑战。

We live longer, so new diseases are important.

人类的寿命正在延长， 所以应对新的疾病很重要。

We're heating up and polluting the planet,

我们的地球正面对着污染 和全球变暖，

so we face a whole host of ecological challenges.

因此，我们面临着一系列的生态挑战。

If we had a million years to wait,

如果我们还有一百万年可以等待，

new proteins might evolve to solve those challenges.

那么新的蛋白质或许 会为我们解决这些挑战。

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

但是我们并没有一百万年可以等待，

Instead, with computational protein design,

相反，通过计算机蛋白质设计，

we can design new proteins to address these challenges today.

我们现在可以设计新型蛋白质 来应对这些挑战。

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

我们的大胆想法是 把生物学带出石器时代

through technological revolution in protein design.

通过技术革命来设计新型蛋白质。

We've already shown that we can design new proteins

我们已经证明我们 可以设计出新的蛋白质，

with new shapes and functions.

有着新的形状及功能。

For example, vaccines work by stimulating your immune system

例如，疫苗通过刺激你的 免疫系统来发挥作用，

to make a strong response against a pathogen.

让其做出强烈的反应对抗病原体。

To make better vaccines,

为了制造更好的疫苗，

we've designed protein particles

我们设计了蛋白质颗粒，

to which we can fuse proteins from pathogens,

我们可以从病原体中融合蛋白质，

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

像这里的蓝色蛋白质， 来自呼吸道病毒 RSV。

To make vaccine candidates

为了制造真正充满

that are literally bristling with the viral protein,

病毒蛋白的候选疫苗，

we find that such vaccine candidates

我们发现这样的候选疫苗

produce a much stronger immune response to the virus

对病毒产生了比以往测试过的

than any previous vaccines that have been tested.

任何疫苗更强大的免疫反应。

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

这一点很重要，因为 RSV 目前是

全球婴儿死亡率的主要原因之一。

of infant mortality worldwide.

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

我们还设计出了新型蛋白质 来分解你胃里的麸质，

for celiac disease

用以治疗乳糜泻，

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

以及其他刺激免疫系统 用以对抗癌症的蛋白质。

These advances are the beginning of the protein design revolution.

这些进展成效标志着 蛋白质设计革命的开始。

We've been inspired by a previous technological revolution:

我们受到了先前技术革命的启发：

the digital revolution,

数字革命，

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

在很大程度上是 受一个地方的推动，

Bell Laboratories.

那就是贝尔实验室。

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

贝尔实验室是一个开放、协作的环境，

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

能够吸引到世界各地的顶尖人才。

And this led to a remarkable string of innovations --

它领导了一系列非凡的创新——

the transistor, the laser, satellite communication

晶体管、激光器、卫星通信，

and the foundations of the internet.

以及互联网的基础。

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

我们的目标是建立能有助于 蛋白质设计的贝尔实验室。

We are seeking to attract talented scientists from around the world

我们正致力于吸引 来自世界各地的天才科学家

to accelerate the protein design revolution,

来加速蛋白质设计革命，

and we'll be focusing on five grand challenges.

我们将专注于应对 5 大挑战。

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

首先，从世界各地的 流感菌株中提取蛋白质，

and putting them on top of the designed protein particles

把它们放置于设计好的蛋白质颗粒上，

I showed you earlier,

就像我之前展示的，

we aim to make a universal flu vaccine,

我们的目标是制造 一种通用的流感疫苗，

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

一次注射就可以起到 终生预防流感的作用。

The ability to design --

设计的能力——

(Applause)

（掌声）

The ability to design new vaccines on the computer

在计算机上设计新疫苗的能力

is important both to protect against natural flu epidemics

对预防自然性流感的流行，

and, in addition, intentional acts of bioterrorism.

以及人为的生物恐怖主义都很重要 。

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

第二，我们要超越大自然 有限的字母表，

of just 20 amino acids

其中只有 20 种氨基酸，

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

转为使用由数千种 氨基酸组成的字母表

using an alphabet of thousands of amino acids.

来为慢性疼痛等疾病 设计新的治疗方案。

Third, we're building advanced delivery vehicles

第三，我们正在制造 先进的药物输送载体 ，

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

以使现有的药物 能够精确定位体内的目标。

For example, chemotherapy to a tumor

例如，对肿瘤的化疗，

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

或者对需要进行基因修复的 组织进行基因治疗。

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

第四，我们正在设计 能在体内进行计算的智能疗法。

and go far beyond current medicines,

远远超越当前医疗水平，

which are really blunt instruments.

现在我们使用的 还是较为迟缓的仪器。

For example, to target a small subset of immune cells

例如，仅针对一小部分免疫细胞，

responsible for an autoimmune disorder,

这些免疫细胞是造成 自身免疫紊乱的原因，

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

从而将其与大多数健康 免疫细胞区分开来。

Finally, inspired by remarkable biological materials

最后，受非凡生物材料的启发，

such as silk, abalone shell, tooth and others,

如，丝绸、鲍鱼壳、牙齿等，

we're designing new protein-based materials

我们正在设计新型蛋白质材料，

to address challenges in energy and ecological issues.

用以解决能源和生态问题方面的挑战。

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

为了实现这一切， 我们正在发展我们的研究所。

We seek to attract energetic, talented and diverse scientists

我们致力于吸引来自世界各地， 处于任何职业生涯阶段的

from around the world, at all career stages,

富有活力、才华横溢、 多样性的科学人才们

to join us.

加入我们。

You can also participate in the protein design revolution

您也可以加入蛋白质设计革命，

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

通过我们的在线折叠和设计游戏， “Foldit”。

And through our distributed computing project, Rosetta@home,

和我们的分布式网络计算项目 rosetta@home，

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

您可以通过笔记本电脑 或安卓智能手机获取。

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

通过蛋白质设计 使世界变得更好是我一生的工作。

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

我很激动我们能够一同携手。

I hope you'll join us,

我期待各位的加入，

and thank you.

谢谢大家。

(Applause and cheers)

（掌声和欢呼）