The wonders of the molecular world animated Janet Iwasa

I live in Utah,

a place known for having
some of the most awe-inspiring

natural landscapes on this planet.

It’s easy to be overwhelmed
by these amazing views,

and to be really fascinated by these
sometimes alien-looking formations.

As a scientist, I love
observing the natural world.

But as a cell biologist,

I’m much more interested
in understanding the natural world

at a much, much smaller scale.

I’m a molecular animator,
and I work with other researchers

to create visualizations
of molecules that are so small,

they’re essentially invisible.

These molecules are smaller
than the wavelength of light,

which means that we can
never see them directly,

even with the best light microscopes.

So how do I create
visualizations of things

that are so small we can’t see them?

Scientists, like my collaborators,

can spend their entire
professional careers

working to understand
one molecular process.

To do this, they carry out
a series of experiments

that each can tell us
a small piece of the puzzle.

One kind of experiment
can tell us about the protein shape,

while another can tell us

about what other proteins
it might interact with,

and another can tell us
about where it can be found in a cell.

And all of these bits of information
can be used to come up with a hypothesis,

a story, essentially,
of how a molecule might work.

My job is to take these ideas
and turn them into an animation.

This can be tricky,

because it turns out that molecules
can do some pretty crazy things.

But these animations
can be incredibly useful for researchers

to communicate their ideas
of how these molecules work.

They can also allow us
to see the molecular world

through their eyes.

I’d like to show you some animations,

a brief tour of what I consider to be
some of the natural wonders

of the molecular world.

First off, this is an immune cell.

These kinds of cells need to go
crawling around in our bodies

in order to find invaders
like pathogenic bacteria.

This movement is powered
by one of my favorite proteins

called actin,

which is part of what’s known
as the cytoskeleton.

Unlike our skeletons,

actin filaments are constantly
being built and taken apart.

The actin cytoskeleton plays
incredibly important roles in our cells.

They allow them to change shape,

to move around, to adhere to surfaces

and also to gobble up bacteria.

Actin is also involved
in a different kind of movement.

In our muscle cells, actin structures
form these regular filaments

that look kind of like fabric.

When our muscles contract,
these filaments are pulled together

and they go back
to their original position

when our muscles relax.

Other parts of the cytoskeleton,
in this case microtubules,

are responsible for long-range
transportation.

They can be thought of
as basically cellular highways

that are used to move things
from one side of the cell to the other.

Unlike our roads,
microtubules grow and shrink,

appearing when they’re needed

and disappearing when their job is done.

The molecular version of semitrucks

are proteins aptly named motor proteins,

that can walk along microtubules,

dragging sometimes huge cargoes,

like organelles, behind them.

This particular motor protein
is known as dynein,

and its known to be able
to work together in groups

that almost look, at least to me,
like a chariot of horses.

As you see, the cell is this incredibly
changing, dynamic place,

where things are constantly
being built and disassembled.

But some of these structures

are harder to take apart
than others, though.

And special forces need to be brought in

in order to make sure that structures
are taken apart in a timely manner.

That job is done in part
by proteins like these.

These donut-shaped proteins,

of which there are many types in the cell,

all seem to act to rip apart structures

by basically pulling individual proteins
through a central hole.

When these kinds of proteins
don’t work properly,

the types of proteins
that are supposed to get taken apart

can sometimes stick together and aggregate

and that can give rise
to terrible diseases, such as Alzheimer’s.

And now let’s take a look at the nucleus,

which houses our genome
in the form of DNA.

In all of our cells,

our DNA is cared for and maintained
by a diverse set of proteins.

DNA is wound around proteins
called histones,

which enable cells to pack
large amounts of DNA into our nucleus.

These machines
are called chromatin remodelers,

and the way they work
is that they basically scoot the DNA

around these histones

and they allow new pieces of DNA
to become exposed.

This DNA can then be recognized
by other machinery.

In this case, this large molecular machine

is looking for a segment of DNA

that tells it it’s
at the beginning of a gene.

Once it finds a segment,

it basically undergoes
a series of shape changes

which enables it to bring in
other machinery

that in turn allows a gene
to get turned on or transcribed.

This has to be a very
tightly regulated process,

because turning on the wrong gene
at the wrong time

can have disastrous consequences.

Scientists are now able
to use protein machines

to edit genomes.

I’m sure all of you have heard of CRISPR.

CRISPR takes advantage
of a protein known as Cas9,

which can be engineered
to recognize and cut

a very specific sequence of DNA.

In this example,

two Cas9 proteins are being used
to excise a problematic piece of DNA.

For example, a part of a gene
that may give rise to a disease.

Cellular machinery is then used

to basically glue two ends
of the DNA back together.

As a molecular animator,

one of my biggest challenges
is visualizing uncertainty.

All of the animations I’ve shown to you
represent hypotheses,

how my collaborators think
a process works,

based on the best information
that they have.

But for a lot of molecular processes,

we’re still really at the early stages
of understanding things,

and there’s a lot to learn.

The truth is

that these invisible molecular worlds
are vast and largely unexplored.

To me, these molecular landscapes

are just as exciting to explore
as a natural world

that’s visible all around us.

Thank you.

(Applause)

我住在犹他州,

这个地方以拥有这个星球上
一些最令人敬畏的

自然景观而闻名。

很容易
被这些令人惊叹的景色所淹没,

并被这些
有时看起来像外星人的地层真正着迷。

作为一名科学家,我喜欢
观察自然世界。

但作为一名细胞生物学家,

我更感兴趣的是
在更小范围内了解自然世界

我是一名分子动画师
,我与其他研究人员

一起创建
分子的可视化,这些分子非常小,

它们基本上是不可见的。

这些分子
小于光的波长,

这意味着我们
永远无法直接看到它们,

即使使用最好的光学显微镜也是如此。

那么,我如何创建

小到我们看不到的事物的可视化呢?

像我的合作者一样,科学家们

可以将他们的整个
职业生涯

都花在了解
一个分子过程上。

为此,他们进行
了一系列实验

,每个实验都可以告诉我们
一小部分谜题。

一种实验
可以告诉我们蛋白质的形状,

而另一种可以告诉我们

它可能与哪些其他蛋白质相互作用

,另一种可以告诉
我们它在细胞中的位置。

所有这些信息
都可以用来提出一个假设,

一个关于分子如何工作的故事。

我的工作是将
这些想法转化为动画。

这可能很棘手,

因为事实证明分子
可以做一些非常疯狂的事情。

但是这些动画
对于研究

人员交流他们
对这些分子如何工作的想法非常有用。

它们还可以让我们

通过它们的眼睛看到分子世界。

我想给你们看一些动画

,简要介绍一下我认为是

分子世界的一些自然奇观。

首先,这是一个免疫细胞。

这些细胞需要
在我们的身体里四处爬行

,才能找到
像病原菌这样的入侵者。

这种运动是
由我最喜欢的一种叫做肌动蛋白的蛋白质驱动的

它是所谓
的细胞骨架的一部分。

与我们的骨骼不同,

肌动蛋白丝不断地
被构建和分解。

肌动蛋白细胞骨架
在我们的细胞中起着非常重要的作用。

它们允许它们改变形状

、四处移动、粘附在表面

上并吞噬细菌。

肌动蛋白也
参与了另一种运动。

在我们的肌肉细胞中,肌动蛋白结构
形成这些规则的细丝

,看起来有点像织物。

当我们的肌肉收缩时,
这些细丝被拉在一起

,当我们的肌肉放松时,它们又
回到原来的位置

细胞骨架的其他部分,
在这种情况下是微管

,负责远程
运输。

它们可以被认为
是基本的蜂窝高速公路

,用于将东西
从单元的一侧移动到另一侧。

与我们的道路不同,
微管会生长和收缩,

在需要时出现,在

完成工作时消失。

半卡车的分子版本是一种

被恰当地命名为运动蛋白的蛋白质,

它可以沿着微管行走,

有时会在它们后面拖着巨大的货物,

比如细胞器。

这种特殊的运动蛋白
被称为动力蛋白,

众所周知,它能够
以几乎看起来像马车的群体一起工作

,至少在我看来,
就像一辆战车。

如你所见,牢房是一个
变化莫测、充满活力的地方,

东西不断地
被建造和拆卸。

但是,其中一些结构

比其他结构更难拆开

并且需要引入特种部队

,以确保
及时拆除建筑物。

这项工作部分是
由这些蛋白质完成的。

这些甜甜圈状的蛋白质

在细胞中有多种类型,

它们似乎都

通过将单个蛋白质拉
过中心孔来撕裂结构。

当这些类型的蛋白质
不能正常工作时

,原本应该被分解的蛋白质类型

有时会粘在一起并聚集在一起

,从而
导致可怕的疾病,例如阿尔茨海默氏症。

现在让我们看一下细胞核,

它以 DNA 的形式存放着我们的基因组

在我们所有的细胞中,

我们的 DNA
都由一组不同的蛋白质照顾和维持。

DNA 缠绕在称为组蛋白的蛋白质周围

使细胞能够将
大量 DNA 装入我们的细胞核中。

这些机器
被称为染色质重塑器

,它们的工作
方式是它们基本上

在这些组蛋白周围搜寻 DNA,

并允许新的 DNA 片段
暴露出来。

然后,该 DNA 可以
被其他机器识别。

在这种情况下,这个大型分子机器

正在寻找一段 DNA

,告诉它它
位于基因的开头。

一旦它找到一个片段,

它基本上会经历
一系列的形状变化

,这使它能够引入
其他机器

,从而允许
基因被打开或转录。

这必须是一个非常
严格监管的过程,

因为在错误的时间打开错误的基因

会产生灾难性的后果。

科学家们现在
能够使用蛋白质机器

来编辑基因组。

相信大家都听说过CRISPR。

CRISPR利用
了一种称为Cas9的蛋白质,

这种蛋白质可以被设计
成识别和

切割非常特定的DNA序列。

在这个例子中,

两个 Cas9 蛋白被
用来切除有问题的 DNA 片段。

例如,可能导致疾病的基因的一部分

然后使用细胞机器

将 DNA 的两端重新粘合在一起。

作为一名分子动画师

,我最大的挑战之一
是可视化不确定性。

我向您展示的所有动画都
代表假设,

即我的合作者

根据他们拥有的最佳信息
认为流程如何运作。

但是对于很多分子过程,

我们仍然处于理解事物的早期阶段

还有很多东西要学习。

事实是

,这些不可见的分子世界
是巨大的,而且在很大程度上还没有被探索过。

对我来说,探索这些分子

景观就像探索

我们周围可见的自然世界一样令人兴奋。

谢谢你。

(掌声)