Synthetic Biology: Principles and Applications - Jan Roelof van der Meer

Summary

简述了合成生物学的基本原理及其应用。合成生物学通过理解生物过程的重建而非解构，以及构建具有新功能的复杂生物过程，来实现对生物体的深入理解。通过标准化生物部件、DNA合成、设计基因组等手段，合成生物学正推动着医药、农业、工业和环境等多个领域的创新。特别介绍了生物报告器的应用，这是一种工程化细菌，能够检测环境中的有毒化学物质，如砷，并在实验室外进行实地测试，展示了合成生物学在环境监测中的潜力和实际应用。

Takeaways

• 🧬 合成生物学是将生物学原理应用于设计和构建新生物部件、设备和系统，与传统生物学的观察、突变分析和解剖方法形成对比。
• 🔬 合成生物学家通过将DNA序列分解为可研究的生物部件，再将这些部件重新组装来构建新的生物功能。
• 📚 合成生物学中的规则和模型类似于电子工程中的逻辑规则，用于预测和控制基因表达和蛋白质行为。
• 🏭 合成生物学的一个核心概念是标准化，类似于电子工程中的插头标准，使得不同实验室和行业能够共同协作。
• 🛠️ 合成生物学的目标是通过重建复杂生物过程来理解它们，以及设计具有新功能的复杂生物过程。
• 🌱 合成生物学的研究活动包括标准化部件制造、DNA合成、基因组设计、最小细胞生产平台、原细胞和人工生命研究，以及Xeno-DNA研究。
• 💊 合成生物学在医疗健康领域具有广泛的应用潜力，包括制药、疫苗、基因疗法、组织工程、益生菌、诊断等。
• 🌾 在农业领域，合成生物学可以帮助改良植物，使其抵抗疾病和干旱，提供更好的动物饲料，并有助于CO2固定。
• ♻️ 合成生物学在环境领域也有应用，如通过工程细菌监测环境污染，进行生物修复和废物处理。
• 🔬 生物报告器是合成生物学的一个具体应用，它们是经过工程改造的细菌，能够感应环境中的有毒化学物质，并通过发光或荧光来报告。
• 🌐 合成生物学的市场价值预计在2016年达到100亿美元，涉及医药、化学品、农业和能源等多个领域。

Q & A

合成生物学的基本原理是什么？

合成生物学的基本原理包括将DNA分解为生物部件，理解这些部件如何协同工作（规则和模型），以及建立标准以促进不同实验室和行业之间的合作。合成生物学家将这些部件重新组合，构建新的或修改过的生物系统。

合成生物学与传统生物学在研究方法上有何不同？

传统生物学通常通过观察、突变创造和解剖来理解生物体，而合成生物学则通过将DNA分解为部件，利用规则和模型来理解这些部件如何协同工作，并建立标准来促进不同实验室和行业之间的合作。

合成生物学中的“生物报告器”是什么？

生物报告器是合成生物学中一种经过工程改造的细菌细胞，它们可以被赋予不同的颜色，如生物发光或荧光，用于检测环境中的有毒化学物质。当这些细胞检测到特定化合物时，会触发产生光或荧光的反应。

合成生物学在环境监测方面有哪些潜在应用？

合成生物学在环境监测方面的潜在应用包括使用生物报告器来检测水体中的有毒化学物质，如砷，以及测量海洋中的石油污染。这些生物报告器可以快速、低成本地提供环境质量的直接测量。

合成生物学在农业方面的应用有哪些？

合成生物学在农业方面的应用包括改进植物以抵抗疾病、耐旱，并提供更好的动物饲料，以及可能帮助固定二氧化碳。这些应用有助于提高作物产量和质量，同时减少对环境的影响。

合成生物学如何帮助生产新的化学物质和材料？

合成生物学可以通过设计和构建具有新功能的复杂生物途径来帮助生产新的化学物质和材料。例如，合成生物学可以用于生产生物能源、生物燃料、大宗化学品、特殊化学品以及创造新型材料。

合成生物学在医疗健康领域的潜在应用是什么？

合成生物学在医疗健康领域的潜在应用包括生产新的药物、疫苗、基因疗法、组织工程、益生菌和诊断工具。这些应用有助于改善疾病治疗、预防和健康监测。

合成生物学中的“底盘”概念是什么？

在合成生物学中，“底盘”是指一个基本的生物体，它可以被用作平台来插入或修改特定的生物学功能。就像汽车制造中的底盘一样，底盘提供了一个基础，可以在上面添加不同的组件。

合成生物学如何促进DIY社区的发展？

合成生物学通过提供简单的生物实验和工具，使得业余爱好者和非专业人士能够参与到生物学的研究和实践中来。这种DIY（自己动手做）的方法有助于普及生物学知识，并激发公众对科学的兴趣。

合成生物学的全球市场价值预计会如何增长？

根据2011年的一份报告，合成生物学的全球市场价值预计从2011年的16亿美元增长到2016年的100亿美元。这表明合成生物学被视为一个具有巨大潜力和重要性的市场。

Outlines

00:00

🧬 合成生物学的介绍与原理

Jan Roelof van der Meer教授在视频中介绍了合成生物学的基本概念和应用。合成生物学与生物学家通常理解生物的方式不同，它涉及到塑料生物或具有特殊特性的生物。教授的目标是解释合成生物学的概念，并与生物学家研究生物的传统方式进行对比。此外，教授还提到了合成生物学中的研究方向，包括他们自己关于合成生物报告细胞的研究，这些细胞可能对环境监测有用。生物学通常涉及观察生物行为，例如通过观察细菌的运动和Daphnia的运动来了解它们的行为。另外，生物学家还通过创造突变来理解生物，例如通过改变Bacillus subtilis的DNA来研究细胞壁的形成。生物学的另一个重要方面是解剖学，包括解剖蜜蜂等生物以了解它们的内部器官如何与细菌相互作用。

05:02

🔬 合成生物学的DNA序列分析与模型构建

合成生物学家通过分析DNA序列来理解生物体的遗传信息。他们将DNA分解为可组装的生物部件，例如编码蛋白质的基因、启动子、核糖体结合位点(RBS)、终止子以及转录因子结合位点等。这些部件可以被单独研究，然后以不同的方式重新组合。合成生物学家还使用规则和模型来理解DNA序列如何协同工作。例如，他们可能会构建一个简单的遗传电路模型，通过逻辑规则（如基因的开/关状态）来预测DNA、启动子、终止子和结合位点如何共同作用。此外，合成生物学还涉及到标准的概念，类似于电子工程中的标准化部件，以促进不同实验室和行业之间的合作。

10:04

🛠️ 合成生物学的目标与研究活动

合成生物学的目标是通过重建复杂生物过程来理解它们，而不是像传统生物学家那样通过解剖。它还旨在促进构建具有新功能的复杂生物过程。合成生物学的研究活动包括制作标准化部件、DNA合成、设计整个基因组、重建复杂现象如细菌的鞭毛合成，以及创建最小细胞和宿主生产平台。此外，还有尝试制造原始细胞和人工生命的研究，以及探索Xeno-DNA，即改变DNA和蛋白质以引入新的氨基酸。最后，合成生物学还促进了生物学与自己动手（DIY）社区的结合，激发了业余爱好者对生物学的兴趣。

15:05

🌱 合成生物学在各个领域的应用

合成生物学在人类健康、动物健康、农业、工业、环境等领域有广泛的应用潜力。在医疗领域，它可能有助于开发新药物、疫苗、基因疗法、组织工程、益生菌和诊断方法。农业方面，合成生物学可以改进植物，使其更能抵抗疾病和干旱，提供更好的动物饲料，并帮助固定二氧化碳。在工业中，合成生物学可用于开发生物能源和生物燃料、大量化学品的生产、特殊化学品和新材料。环境方面，合成生物学可以帮助开发生物传感器、生物修复和废物处理技术。

20:07

🔍 生物报告细胞在环境监测中的应用

生物报告细胞是一种经过工程改造的细菌，可以用于检测环境中的有毒化学物质。这些细胞内部有一个小电路，可以识别并结合进入细胞的化合物，并通过感应蛋白触发新蛋白质的合成。这些新蛋白质通常能够发出光或荧光，从而发出信号。例如，研究人员开发了能够检测砷的细胞，这对于检测地下水中的砷污染非常有用。通过与ARSOLUX公司的合作，他们开发了一种便携式发光计，可以在现场测量水样中的砷含量。此外，生物报告细胞还被用于测量海洋污染，通过检测油中的化合物如烷烃、溶剂和芳香烃来评估海洋污染的程度。

25:08

📈 合成生物学市场的预测与展望

合成生物学预计会成为一个全球性的重要市场。2011年的一份报告预测，到2016年，合成生物学在制药、化工产品、农业和能源等领域的全球市场价值将达到10亿美元。合成生物学的应用前景广阔，一些应用已经触手可及，例如用于测量环境质量的生物报告细胞。这些应用不仅具有潜在的实用性，而且可以立即投入使用，展示了合成生物学在构建而非解剖生物方面的潜力。

Keywords

💡合成生物学

合成生物学是一门结合生物学和工程学原理的学科，它涉及对生物组件的设计和构建，以实现特定的功能。在视频中，合成生物学被用来解释如何通过构建而非单纯的解剖来理解复杂的生物过程，并且它还涉及到创造具有新功能的复杂生物过程。例如，通过合成生物学，研究人员可以设计出能够检测环境中有毒化学物质的生物报告器细胞。

💡生物报告器

生物报告器是合成生物学中的一种应用，它们是被设计用来对特定环境刺激做出反应的微生物细胞。在视频中，生物报告器被用来检测水中的砷和海洋中的石油污染，通过发出光或荧光信号来指示污染物的存在。这种应用展示了合成生物学在环境监测中的实用性和即时性。

💡基因序列

基因序列是指DNA分子中核苷酸的排列顺序，它是遗传信息的基本单位。视频中提到，通过分析基因序列，研究人员可以理解生物体的遗传蓝图，并从中识别出蛋白质编码区域、RNA、调控元件等重要特征。基因序列的分析是合成生物学中设计和构建生物组件的基础。

💡突变

突变是指生物体DNA序列的改变，这些改变可以是自然发生的，也可以是人为诱导的。视频中提到，通过创造突变，研究人员可以研究细胞壁合成等生物学过程，从而理解正常细胞功能和突变对生物体的影响。

💡基因工程

基因工程是一种技术，它涉及对生物体的基因进行直接操纵和修改，以实现期望的生物学功能或特性。视频中提到，合成生物学与基因工程有相似之处，但合成生物学更侧重于通过构建和标准化的生物组件来设计复杂的生物系统。

💡基因电路

基因电路是合成生物学中的一个概念，它指的是在细胞内设计和构建的一系列相互作用的基因组件，这些组件可以协同工作以执行特定的生物学功能。视频中通过一个简单的例子解释了基因电路如何通过一系列规则来指导细胞行为。

💡模型

在合成生物学中，模型是对生物系统行为的数学或逻辑表示，用于预测和解释生物过程。视频中提到，通过构建模型，研究人员可以模拟基因电路的行为，理解不同基因组件如何相互作用。

💡标准

标准在合成生物学中指的是一套共同遵守的规则和组件，以便不同实验室和行业能够协作并重复使用相同的生物组件。视频中通过类比电气工程中的插头标准来解释合成生物学中的标准概念，强调了标准化对于合成生物学发展的重要性。

💡最小细胞

最小细胞是合成生物学中的一个概念，指的是通过去除非必需的生物组件来创建的简化版细胞。视频中提到，研究人员试图设计最小细胞作为生产平台，以便更容易地插入和测试新的生物组件或路径。

💡异源DNA

异源DNA是指在DNA序列中引入非自然或非标准的分子，如不同的氨基酸。视频中提到，通过异源DNA，研究人员可以赋予蛋白质新的功能，这是合成生物学探索新生物学功能的一种方式。

Highlights

合成生物学是将生物学原理应用于工程和技术领域的学科，它通过合成方式设计和构建新的生物部件、设备和系统。

合成生物学与传统生物学的不同之处在于其更侧重于构建而非仅是分析生物系统。

合成生物学的应用领域包括环境监测、医疗健康、农业、工业生产等。

合成生物学家通过构建生物报告器细胞，用于监测环境中的有毒化学物质。

合成生物学研究涉及基因序列的解读、生物部件的标准化以及复杂生物过程的重建。

合成生物学利用模型和规则来预测和控制生物系统的运作。

合成生物学的目标之一是理解复杂生物过程，通过重建而非仅是解构。

合成生物学的另一目标是构建具有新功能的复杂生物过程。

合成生物学的研究活动包括标准部件的制作、新模型的开发和复杂工程策略的探索。

合成生物学在DNA合成领域的进步使得基因工程变得更加快速和简便。

合成生物学尝试设计最小细胞和宿主生产平台，类似于汽车制造中的底盘概念。

合成生物学还探索制造原细胞和人工生命，以帮助理解生命的起源。

合成生物学的应用之一是利用生物报告器检测砷污染，这对全球许多地区的居民具有重要意义。

合成生物学的另一个应用是在海洋污染监测中使用生物报告器来检测油类污染物。

合成生物学的市场价值在2011年估计为16亿美元，并预计在2016年增长到100亿美元。

合成生物学的实践案例展示了其在环境监测和污染控制中的潜力和即时应用的可能性。

合成生物学的发展不仅推动了科学研究，也吸引了业余爱好者和DIY社区的兴趣。

Transcripts

Hello, my name is Jan Roelof van der Meer, I'm a

professor in microbiology at the University of Lausanne in

Switzerland. Today I would like to talk to you about

synthetic biology. About the principles of synthetic biology,

and some of the applications. Some of you may have very different

perspectives and ideas about what is synthetic biology.

You may have heard of the word, you may have associated

it with plastic organisms or with organisms doing various

strange characteristics. But probably, this is not what

synthetic biology really is. So my goal of today is

to explain to you the concepts of synthetic biology

and contrasting them to the normal way that biologists

work when they try to understand living beings. After

that, I will tell you something about research directions that

are ongoing in synthetic biology, and I would like to explain

some of our own work, which is about synthetic bioreporter

cells that we think are useful for environmental purposes.

So, if we think about biology, it's really about understanding

living organisms in all their aspects. So you may think that

biology is about going out into the jungle and looking at

elephants, but as a microbiologist, we often look just at

bacteria, microscopic organisms. So what you see here

is this small growth chamber that we developed in order to

look at the behavior of single cell bacteria that you can see

here as these small rods. And what this small instrument is

doing is that we can feed the bacteria from the left side

and then look at their behavior on the right side. So it's really

very simple in the sense of looking at what the organisms are

doing. Biology often uses observation, just observational

techniques to study behavior. So here on the left side,

you can see for example how bacteria, even though they're

extremely small, use a flagella to move themselves forward

in search of nutrients or conditions that they have. You can see

the spirally movement of the flagella that propels the cells in one

direction, and if they want to change the direction, you can see that

the flagella become disordered and they can rotate the cell to go in

another direction. You can see on the other image here more closer,

that this is an observation of a single Daphnia individual. And Daphnia

is a small water creature that lives in most freshwater habitats.

And what you see here is the movements of its legs and of the

heart and of the internal organs. So the organism is sufficiently

transparent that you can keep it under the microscope. Here we

keep it in a small cage, where the organism sits and is fed

with fresh water. And we can observe how it reacts.

So observation really is one of the critical tools that biologists

can use. Another tool that biologists use a lot is understanding

from the creation of mutations. So what are mutations?

Mutations are changes that we make in the DNA, the hereditary

material of organisms. Again here you see a very simple

example, on the left side you see the cell of a wild bacterium

called Bacillus subtilis. Which is a bacterium that normally

dwells in the soil, it can make spores, it knows how to

survive very well. In order to understand how this cell

divides, researchers have made mutants that cannot make

proper cell walls. So for example, if you look at this particular cell

here, it's completely round and blown up because it carries

a mutation in a gene that is essential to make the cell

and that otherwise maintains the cell as a nice rod shaped

structure that you see on the left. So by knowing where these

mutations are, we can try to understand how the organism

organizes itself and makes this cell wall. The third important

aspect that biology uses is what we call dissection.

So we like to take things apart in biology in order to understand.

This can be an anatomic dissection, like you see here for a bee where

investigators of our own department dissect the bee to

understand how the bee gut and the internal organs of the bee

work. And how they interact with bacteria that live in the

gut of the bee. So you can see here, a researcher preparing

the gut of the bee in order to understand this. It's not only

anatomic dissection that biologists use, but more and more, we

also use genetic dissection. So we like to understand

what the DNA is made of in every living organism and how

this contributes to the whole body plan and how the whole

functioning of that particular organism. Maybe you have

seen genetic dissection of DNA before, what you can see here

for example, is a culture of cells on the left, it looks like if you

have a soup, a turbid soup. This is because the soup

culture contains millions and millions of bacterial cells

that you can break open by lysis and then you can isolate

the DNA that in solution looks sort of like this fluffy solution.

This fluffy material, this white-ish material. If you put this

white-ish material under a microscope, here under the

atomic force microscope, you can see that it forms sort of

a chain of pearls that you can observe. And you can draw certain

conclusions from it, but more importantly, for DNA, we often look at

the gene sequence. So we take the DNA apart, we determine

base by base what the DNA looks like. And that's shown here in

the trace below, where every peak that you see in a different

color, in red or green or blue, means a different base

of which the DNA is made up. Now if we take all that sequence

together, so then we try to convert it to code, just the

code of A, C, G, and T, you can get a very nice

and thick book. This is the start, if you like, of a

genome sequence of a single bacterium. This bacterium

doesn't have a very big genome, it's only like 6 million characters.

But if you think about this page containing 2000 characters

per page, then you would still need 3000 pages to print that whole

bacterial genome, which is quite a thick book. And if you think

that the human genome is a thousand times bigger, then

that would be a very big genome. So normally we don't

print that out, because it would take too much space.

Now the real goal in biology, in particular molecular biology is to

understand what does this sequence actually mean. All

these letters that are there. What do they do? How can this be the

important plan for the bacterium or the living organism that

is there? So what we often do is we try to gaze into the

sequence and do an analysis of important features that this

sequence can contain. So as you know, the sequences contain

for proteins, for RNAs, there's signals on the DNA that are

important to direct certain proteins to actually read the

instructions in the DNA and form the parts for the cell that are needed.

So what is really important is that we understand what

such a DNA sequence means. And as I said, this could mean

a really big sequence. So when we look at this particular

part, you can see some of the things that biologists

try to interpret. This is the case of a bacterial genome.

So what we are looking at here in what is called reading

frame, is actually the region that is needed for the cell to

recognize, oh this is the part of the DNA where I have to

make an mRNA and then a protein. A reading frame has to

have a start, like here is shown at the ATG, that's the start of that

reading frame. It's a signal to start building the protein

where it's needed. But then there are also other parts that are

needed, for example, what is shown here as an RBS.

This is a site that is recognized by the ribosomes, the

factories that produce the proteins, to begin the

synthesis of a protein. And then there are often other parts

on a sequence that do not code directly for a protein, but

are important for other proteins to know where to start

doing the task they have to do. So for example, here in green

is the protein binding site, it's a transcription factor binding site

that directs the machinery toward expressing that gene.

Next to it is a promoter sequence, that is a signal for the RNA

polymerase to start transcribing that gene and so on and so forth.

Now this is really the basis, or this is really where biology

ends and where synthetic biology starts. Because synthetic

biologists start to interpret this sequence in a different

schematic way. So one of the concepts of synthetic

biology is really that you break the DNA down into

biological parts. This can be DNA parts that you can

assemble in a particular way, or it can be protein parts

if you want to profit from these protein parts. So if we

look again at this sequence that I just showed you in a

different way, in a very schematic way, then it may look for a

synthetic biologist like this. A gene, so a coding region that is

needed for a protein, will look like a small arrow here in green

or there in brown. That codes for protein 1 or protein 2, depending

on what we need. The synthesis of those genes are driven by

promoters that we display by different other arrows, here

in small black arrows, and we have important signals for the

ribosomes to start the translation of such proteins that are

listed here as RBS. And there may be other things that a

synthetic biologist needs like here, a binding site for a regulatory

protein, and here a terminator that's a signal for the RNA

polymerase to stop. So it's really important to try and

understand. We can decompose the sequence into parts

that we can study as they are in a living organism in

the particular way that they appear, but we can also move

them into different parts. So if we take this sequence

apart, then we see really what the circuit parts are so that

the synthetic biologist would need. So we may need a part

for genes, we need a part for ribosome binding sites,

promoters that are signals, terminators that are signals,

binding sites for transcription factors on the DNA, these are the

parts that we need in order to assemble something. The

protein part that we need would be a structural protein,

a regulator protein that we can see that is important to

signal the cells "yes now you start transcribing that gene

or not." We need transcription factors, we need sensory

proteins depending on what we actually want. So it's really

important to realize that we can go from the sequence

to the parts, we can study the parts and then we can put them

back together in a different way. Now the second concept that

is very important for synthetic biology is rules and models.

So we do not only like to dissect the sequence and know the

exact sequence of the A, C, G, and T's in the genome of an

organism or a part of DNA that we want to construct,

but we want to understand how does this sequence work

together. So which are the rules that the cell is following

in order to make this sequence functional? So for that, synthetic

biology uses certain rules. This could be logic rules like that gene

is on or that gene is off. It could also be models like shown here

in the back, that tries to predict how a particular stretch of

DNA and promoters and terminators and binding sites

is working for the cell. Now if we go back to that same

DNA circuit, the same stretch of DNA that we have

seen before, with the two genes in green and in brown.

And the different parts that are needed to operate this particular

gene circuit, then it means for the cell the following, you can see that

in steps 1, 2, and 3. The first signal for the cell so that it starts

to interpret this DNA sequence is that it will try to transcribe

this particular gene. It does that because there is an RNA

polymerase coming. The RNA polymerase starts at

the promoter and then transcribes that gene until

it reaches the terminator. This mRNA is then translated

into a protein that you can see here schematically in green.

What this protein is doing is that this protein will bind

to the DNA at the particular site that is here in green.

Now that protein's not just any protein, it is a sensory

protein with also activating functions, so it is capable

of sensing for example, a particular chemical that

interacts with this protein and then tries to attract

RNA polymerase again, but to a different promoter.

So what this protein is now doing is that it attracts

RNA polymerase, but to a promoter that is here.

And then when RNA polymerase is there, it will then transcribe that

gene and make that particular protein. So this small

schematic structure is actually giving some instructions

to the cell, start here automatically, make a protein, bind

that protein that can intercept that signal, and then transcribe

another protein. So a very simple thing that follows a certain set of

rules. You can put these rules in a kind of model if you like.

If you have these simple circuits, you can sort of by

modeling, try to predict what they're going to do. Here's an

example of two simple circuits, in one case we have the

two genes that are located in the opposite direction.

In the other case, we have the same genes but located

next to each other. Now the rules that this small circuit

says is that this particular gene codes for a protein

that will then inhibit the transcription of the other gene

here. So in one case, this protein will inhibit its own synthesis

and the gene the gene that is in yellow behind it, in the other

case it, it cannot inhibit its own synthesis because it is not

binding there, it's not influencing this particular promoter

that would transcribe itself. Now the model now would predict

that in the case where you have this feedback, where FB means

feedback loop, then this would be dependent on a signaling

molecule, that is in this case arsenic. And as a function of the arsenic

concentration that is shown here below, you can see that

the more arsenic you add to the system, the more

of this protein ArsR you get. And the more of this protein

GFP that you get. In the case of the uncoupled systems,

so UN means uncoupled here, then this gene is not

under its own control, but it's under the control of something

else. You can see that it's always produced at a constant

level, which is independent of the concentration of in this case,

this arsenic or AsIII. But the other protein is still under

the control of this AsIII, so as you can see here, this increasing

amount when the concentration becomes higher. So this is

a simple model, it's a very simple genetic circuit

as we call it. It gives a set of instructions to the cell and the

cell will carry out these instructions if it is properly equipped.

The third concept of synthetic biology is really standards.

Standards? That sounds very, very weird. Why would you need

standards in biology? Well, think about it. Synthetic biology has

a fair amount of relation to electrical engineering, where people were

working in the beginning with electricity and trying to harness

electricity in forms that are useful. Like cameras, like

televisions, and so on. So the industry and the people had

to adopt certain standards that we now know as electrical

plugs. Now the electrical plug may still be different between Europe

and the U.S., but the essence is that there is an electrical

plug you can plug something in there and it gains the

electricity and can work. In synthetic biology there is a similar

concept in order to try to make it possible that people from

different laboratories and different industries can work

together on the same parts. So maybe we are thinking

about standards for gene expression. But how would that

look like? It's not electricity, it must be some biological

equivalent of electricity. And the plugs? What could they be?

They could be small fragments like here, promoter sequences

that can be adopted into one system or another system.

So standards is really an important part for synthetic

biology. Now having explained all this, what is synthetic

biology really about? So what is synthetic biology hoping

to achieve? There's two main things really, at this point.

One is that we can understand complex biological

processes not by dissecting them as normal biologists do,

but by reconstructing them. So we take parts and we

build something that is more complex, like here schematically shown

for Legos. It looks very much like Legos. So understanding

biological processes not by dissection but by their

reconstruction. The second thing that has appeared in

synthetic biology and that is maybe not so different as

people may know from genetic engineering or so

is to facilitate the construction of complex biological processes

that carry new functionalities. Not just producing one protein

but producing a complex pathway that you engineer

into the cell that was not previously possible.

So these two things are really what synthetic biology

is nowadays trying to accomplish. The engineering

idea, as I said, is really rather similar to what electrical

engineers do. They have their parts, they can be small transistors,

transformers, capacitors that they put together on an electrical

board. These electrical boards, if you put them into your computer,

can give your computer certain instructions. Biologists

and synthetic biologists are trying to do the same.

Take biological parts with some rules, models, and

engineering, we put them together. And then we

try to verify what this construction really is doing and what it

means. Now current research activities in synthetic biology

go consequently in all directions, I would say. There are

groups that work on making standardized parts, making

new models, trying to come up with complex engineering

strategies to put these parts together. That is really

important, because if we want to play with parts, we

actually need to have parts. So the more parts we

have, the better they are characterized, the better we

can produce new structures in synthetic biology. The

second part of synthetic biology has really started off with

DNA synthesis. So previously in genetic engineering, it was really

difficult to make mutations and really cumbersome

and took a lot of time. Now there are DNA synthesis

companies and biologists will simply write down their

sequence, send it by their computer to the DNA

synthesis company who will actually make the construct,

and that facilitates largely to put parts together in a

particular way. So consequently, there are people who try to

design whole genomes, which is still an important and challenging

task. Because we do not understand all the rules very well

to actually be able to put genomes together. In some

cases, people also use genome parts like complex

phenomenon that the cell does. If you remember the

example of the swimming cell, so the flagella synthesis

even for a bacterium takes a lot of power, it's a very

complex process with many proteins. So that's

something that a synthetic biologist may try to reconstruct.

The third thing is something that looks really bizarre

if you think about it. It's the production of minimal cells

and host production platforms, so synthetic biologists have

adopted this terminology that's called "Chassis," almost like a

car factory. You have your chassis that you can put in

this kind of chair or that kind of chair, and it doesn't

really matter because the car is still running. So the

same idea appears for biology as well. You can make

bacteria or yeast that are just a chassis needed to make

the motor for the cell. And everything else you can plug

in, colors, pathways, things and so on. So for that, very often

people find that the living beings that exist naturally are

way too complex. They contain viruses, they contain things

that you wouldn't really need, and that is why they want

to design minimal cells that have been devoid of all

the parts that are not really needed. A fourth direction

in synthetic biology really tries to go even beyond it,

that is trying to make protocells and artificial life.

There is a huge interest in trying to understand where is

life coming from. We do not know, but synthetic biologists

may be able to recreate certain life forms and that

would help enormously to try and understand where is

life coming from and what are the different paths that can

lead to life. Finally, there's a lot of effort in what's called

Xeno-DNA, and this may be sort of your fantasy dream

strains of DNA. But what it's really about is that biologists

and synthetic biologists are saying, you can alter DNA,

you can alter proteins, in that you incorporate different types of

amino acids that the cell normally doesn't like, but it could be

really important to try to incorporate all these into

proteins because it could give new functionalities to

proteins that we cannot currently make. So this is the

xeno-DNA/biology. And finally, there's an important point that

comes with synthetic biology that allows biology to

attach to a do-it-yourself community. So many people

also amateurs become interested in biology because

of the efforts in synthetic biology. Trying to understand

biology, making simple instruments that you can use

in organized groups and so on, to try and understand

biological phenomenon. So this is really an overview

of the general research activities in synthetic biology.

I would like to pick just one particular application.

To give you some idea of things that people are dreaming of,

and this is obviously one of the things where you may say,

okay will these dreams finally come true? But this is a bit of

marketing, if you like, by the biologists and the engineers

that are behind it. So there's a lot of hope that synthetic

biology will be able to help producing new things that

will be useful for human health, animal health, there's obviously

a lot of money going into it. In terms of pharmaceuticals, vaccines,

maybe gene therapy, tissue engineering, probiotics, diagnostics,

and so on. Another area of importance is agriculture.

Try to improve plants that are resistant to diseases,

resistant to drought, that give better feedstocks for animals,

that can maybe help sequestering CO2, chemical production,

diagnostics. Then there are things in industry, you may have

heard about bioenergy and biofuels. Things that can become

very important if synthetic biology is able to create better

organisms that do these kind of conversions with higher

efficiency. Production of bulk chemicals is very important

because maybe at some point, we'll run out of oil and

we need alternatives to actually produce the chemicals

that we need daily. Specialty chemicals, new materials,

people are thinking about building DNA and proteins together

to get new kinds of materials that might have properties that

we have not seen before. And there's also applications in

the environment, like biosensors, bioremediation, waste

treatment that may be helped by engineering specific

organisms that do tricks that we cannot normally achieve

in the natural conditions. So let me explain to you

just about one of the things that we do in our own

lab, which is called bioreporters. These are really

very, very simply engineered bacteria cells. Bacterial

cells that are not pathogenic, harmless in the lab.

And what we can do is that we can equip them with different

colors like here, this is called bioluminescence, it's really

a cell that gives off light. Or with fluorescent colors,

you shine light on them and they produce another

color back that you can measure. Or just regular

colors like blue, red, green, and so on. The idea

with these bioreporters, as we call them, is that the cell

can signal for us the presence of, for example, a toxic

chemical in the environment. And then what the cell is doing is

it has a small circuit inside, so it will recognize the compound

that will diffuse inside the cell and then this compound

is bound again by one of these sensory proteins that I talked

to you about before that can bind the DNA and can direct

the synthesis of a new protein in the cell. And the new

protein is often one of these proteins that we have seen

here, that gives off light or fluorescence and so forth.

So we think that these are very simple cells that can do

very useful tricks for us, because they can help us to make

analytical devices to sort of interrogate parts of the environment

where we think there is contamination that may occur.

One of the systems that we have been working on is

to construct cells that would detect arsenic. So

you know arsenic from the novels of Agatha Christie,

it's a really nasty toxic chemical. But unfortunately,

it has not only been used in novels of Agatha Christie,

but large areas in the world are contaminated with arsenic

from natural resources. So it's an abundant metal

that exists in the earth's crust and can come up in the ground

water. And people like here, shown in this picture in a village in

Bangladesh, suffer enormously because they do not know

if the drinking water that they take from their household

pumps is actually contaminated with arsenic or not.

So we sat together in the lab and with a small

spin off company called ARSOLUX, that is a collaboration

of the Helmholtz Institute in Leipzig in Germany, to make

bacterial systems that would be able to measure

arsenic in drinking water. And then could be used

on the field to measure the water that comes from the

pumps and analyze this for arsenic. So what we do is

we make small glass vials, and you can see here

sort of a powdery stuff. This powdery stuff is really the

bacteria that are dried inside such a vial. The vial is

closed with a stopper, and that's important because that

makes it a closed system and the bacteria cannot

escape. We inject the water directly through the

stopper inside it, this reconstitutes the bacteria, as you can

see here. It makes this sort of watery suspension, if

there is arsenic in this water, the bacteria will react

to it and will start to glow. So they will make this famous

bioluminescent signal that you cannot see by eye unless

you are in a very dark chamber. But you can very easily

do this by putting these small vials into a small instrument that's

shown here, that is called a luminometer. This is a

portable luminometer that we can use in the field.

It has a battery capacity, you close the cap, you wait

a little while, and it measures the light that comes from

the cells. So what we have been able to do is, if we are

in such villages, then we can sample all the wells from those

different households. And that is really the problem, that they don't

have a central drinking water supply, but individual

households are pumping and you have to test all that

water. And not just once, but multiple times. So what we can do

is go into such a village, fill all the different vials that are

necessary for each of the pumps. Fill them one by one,

and then wait until the cells react, and then measure them

one by one by one. And in an afternoon, you can

measure all the water wells in the whole village.

Obviously if you try to do such a test, it's very

important that you can actually show that this is working.

So in the first test that we tried to do, this was done in Bangladesh

and in Vietnam, in different settings with different types of

ground water. We compared that at the same time, the

response from our engineered bacterial cells with the response of

classical chemical analytics by ICP-MS, or with

atomic absorption spectrometry. And as you can

see here, there's a very good dependence between the

signal that's given by the biosensors and the signal

that is given by the chemistry. So there is almost

a one to one ratio of the concentration that you measure

by chemistry and with the biology. And that tells us that this method is

potentially very good and very interesting because

the bacteria multiply by themselves, so to produce such a

biosensor is extremely cheap and doesn't require a lot of

engineering. Whereas to make a GC, MS or atomic

absorption spectrometer, it costs a lot of money

and you cannot deploy it in the field. So that is why

we think that this test could be very interesting

to do this. As another example, we use bioreporters

to measure pollution at sea. So here we engineered

a set of bacterial reporters that could measure different

compounds that come off of oil, like alkanes, solvents,

basically aromatic hydrocarbons. For this we worked together

with the Dutch government on an exercise in the North Sea.

The Dutch Government has what is called responder

vessels, they go out whenever there is an oil pollution and

they scoop the oil and bring it back to the refinery if

they can. But much of the oil, particularly smaller spills, go

undetected and floats there. And nobody really knows

how dangerous this can be. So what we set out to

do with these responder vessels is that we got permission

to actually make an artificial spill out in sea with a limited

amount of crude oil. And then we went onboard with our

small portable luminometer that you see here again,

the different cell lines in the vials that we can directly

incubate with the sea water to try and measure

what is the oil pollution that really occurs at the sea.

This sampling was quite challenging, as you can imagine,

we had to go out with a rubber boat from the responder

vessel to actually approach the oil slick, that you can see for example

here. Because the ship itself is so big that it cannot

go into the oil slick, because otherwise it would be

horribly contaminated as well. So here is an example

of the results that we found in these exercises.

Again, in the top you see the chemical analysis, and in

the bottom, you see the analysis of what we call the

reporter cells that were done onboard. The chemical

analysis was obviously extremely good, but it took two

months to actually get to that. Whereas the bioreporter

signals could be obtained directly onboard the same

afternoon. So here is shown the results of two

experimental spills, we had one opportunity in 2008.

And one opportunity in 2009. And then there are the spills

that we encountered on the way, because the North

Sea is a very busy traffic route. And ships from time

to time, they clean their insides and they throw away overboard

some oil, which we can also analyze. So importantly,

what you can see here in the diagram below with the different

colors is the different parameters that we measured

with the reporter cells. So you can see that in all

cases, our samples from the sea water that were far

below the oil slick that we measured important concentrations

of toluene, benzene, methylene, alkanes, etc ...

So that told us again that what we measured with these

cell lines is very, very relevant and can help to address

the situation of samples at the site immediately. And we

hope that these sort of results are convincing to the

authorities to give permission and perhaps to companies,

to say, oh this is an important way of trying to analyze

and apply synthetic biology efforts. So finally, I would like

to give you sort of a prediction or report. So this is a report

that was commissioned by the European community

to estimate the global value of the market for synthetic

biology. This report was done in 2011, and obviously

these things are always a bit predictive in the sense that

maybe they're not too conservative, but you can see that

the estimates for 2011 were already $1.6 billion USD in various

fields like pharma, chemical products, agriculture, and

energy. In 2016, it's rising up to $10 billion. So this

is really something that everybody has high hopes, that

synthetic biology is going to be a globally important market.

I hope that I have shown you a little bit about how synthetic

biology works, how the concepts work, with the bottom up

construction, not the dissection and destruction of organisms,

but taking parts and building something again. Synthetic

biology has many useful applications, potentially useful

and that's how the research is going. Some of the things may not

make it in the end, whereas other things come surprisingly

and will in the end deliver important results. Several results

are within close reach, so it's not something that we have to

wait 25 years to deliver. No, no, there's important applications

and some of them, like we demonstrated with the small

bioreporter cells to measure the environmental quality

can be used immediately. Thank you very much for your attention.