Synthetic Biology Overview • iBiology

1 00;00;11;15 00;00;13;18 Hi, my name is Victor de Lorenzo,
2 00;00;13;21 00;00;15;22 and I'm the director of a practical course
3 00;00;15;24 00;00;18;29 that is taking place in the facilities of the EMBL,
4 00;00;19;02 00;00;21;24 sponsored by EMBO on synthetic biology.
5 00;00;21;26 00;00;23;26 And that is the basis of the various videos
6 00;00;23;28 00;00;25;27 that you are going to see in this series.
7 00;00;26;00 00;00;28;05 As this course is about synthetic biology
8 00;00;28;06 00;00;29;28 is fair to start by the question
9 00;00;30;00 00;00;32;22 "what is synthetic biology?" and how it relates
10 00;00;33;00 00;00;35;24 to other areas of biology or science in general.
11 00;00;36;12 00;00;38;20 Well, the term synthetic biology has been around
12 00;00;38;23 00;00;41;20 for a while and as early as in 1912,
13 00;00;42;07 00;00;44;16 someone proposed the term to describe
14 00;00;44;19 00;00;47;04 a number of interesting phenomena perhaps
15 00;00;47;07 00;00;49;20 during that time a different meaning.
16 00;00;50;04 00;00;52;01 But, keep also in mind that
17 00;00;52;04 00;00;54;15 synthesis is the counterpart of analysis
18 00;00;54;19 00;00;57;03 and in science we have these two main tools
19 00;00;57;08 00;00;59;05 to address reality and to
20 00;00;59;08 00;01;01;14 decipher the complexity that we find
21 00;01;01;17 00;01;03;11 in all types of natural phenomena.
22 00;01;03;20 00;01;06;14 To the point that there's a famous quotation
23 00;01;06;17 00;01;07;28 by Richard Feynman
24 00;01;08;01 00;01;11;09 saying that "What I cannot create I do not understand."
25 00;01;11;14 00;01;14;11 Meaning by that creating something
26 00;01;14;15 00;01;16;24 is the ultimate proof of understanding.
27 00;01;17;09 00;01;19;16 Well, what does all this have to do with biology?
28 00;01;20;09 00;01;23;01 Today, biology has two pillars,
29 00;01;23;03 00;01;26;19 or, two main pillars. One of them is evolutionary theory
30 00;01;26;26 00;01;29;23 as it was posed by Darwin a time ago.
31 00;01;29;27 00;01;32;27 And, then refined and materialized through a
32 00;01;33;00 00;01;35;17 molecular biology, modern genetics and all the rest of it.
33 00;01;35;22 00;01;37;09 And, the other big pillar
34 00;01;37;11 00;01;40;10 is what is called the central dogma of molecular biology.
35 00;01;40;12 00;01;42;04 That DNA contains all the information
36 00;01;42;05 00;01;43;24 that is transmitted faithfully,
37 00;01;43;25 00;01;45;29 all the way to proteins then to metabolism.
38 00;01;46;13 00;01;48;11 But, let us keep in mind that
39 00;01;48;18 00;01;52;00 knowing the origin of things, and this is what evolutionary theory
40 00;01;52;08 00;01;56;14 is about, may not tell you all the details on how
41 00;01;56;19 00;01;58;13 that very same thing works.
42 00;01;58;15 00;02;01;02 So, when we find an object we can raise the question,
43 00;02;01;04 00;02;02;16 of where the object comes from?
44 00;02;02;18 00;02;05;00 And this is business of evolutionary biology,
45 00;02;05;07 00;02;08;09 but, I insist that in many cases that is not sufficient
46 00;02;08;11 00;02;11;10 to understand how biological objects work.
47 00;02;11;27 00;02;13;08 So, why is that?
48 00;02;13;10 00;02;15;18 Well, there are various approaches
49 00;02;15;19 00;02;16;19 to answer this question.
50 00;02;16;20 00;02;19;05 The one that is the tenet in contemporary biology
51 00;02;19;11 00;02;22;14 is this concept of tinkering as it was proposed
52 00;02;22;20 00;02;24;15 by Francois Jacob a time ago.
53 00;02;24;23 00;02;29;07 And, under this frame the idea is that biological systems
54 00;02;29;20 00;02;33;28 come to work because they take advantage of any
55 00;02;34;08 00;02;38;24 property of any material at hand to build a new function.
56 00;02;39;05 00;02;43;08 By that token, what happens is that in every stage of evolution
57 00;02;43;17 00;02;46;29 every novelty that appears
58 00;02;47;05 00;02;49;05 to fulfill a given purpose
59 00;02;49;07 00;02;52;16 might remain as such or might be eventually co-opted
60 00;02;52;18 00;02;54;00 to do something completely different.
61 00;02;54;14 00;02;58;20 So, sometimes in biology, biologists face the problem
62 00;02;58;29 00;03;01;25 that we observe a complex phenomenon going on
63 00;03;01;29 00;03;05;07 and what we try to determine how that phenomenon
64 00;03;05;09 00;03;07;08 mechanistically works.
65 00;03;07;15 00;03;10;08 Then we find sometimes an inexplicable complexity.
66 00;03;10;10 00;03;13;15 And in many cases this is the result of evolution,
67 00;03;13;17 00;03;14;22 because evolution has picked up
68 00;03;15;04 00;03;18;05 functions, materials here and there, and eventually
69 00;03;18;07 00;03;20;11 something useful happens that can be selected
70 00;03;20;13 00;03;22;22 for the next stage in the process.
71 00;03;22;29 00;03;26;00 This is very graphically represented by
72 00;03;26;05 00;03;28;23 the cartoons by Rube Goldberg,
73 00;03;28;28 00;03;32;17 and in this case what you have here is a situation
74 00;03;32;24 00;03;36;19 that I find interesting, and is the necessity, or the function to
75 00;03;36;27 00;03;40;10 wake up a gentleman in bed, is brought about because
76 00;03;40;13 00;03;43;25 occurrence of a number of successive actions that start
77 00;03;44;00 00;03;46;10 with the sun rising in a window and then
78 00;03;46;15 00;03;48;22 after a while, and a number of events,
79 00;03;48;25 00;03;51;28 then the gentleman is woken up.
80 00;03;52;01 00;03;56;08 So, well sometimes in nature we find the same situation.
81 00;03;56;10 00;04;00;27 all these events that we observe them, that we may
82 00;04;00;29 00;04;05;12 make a real sense of why they came about. But in reality,
83 00;04;05;14 00;04;09;16 in many cases we don't really understand why they work
84 00;04;09;18 00;04;11;05 as they were and we even wonder
85 00;04;11;07 00;04;12;26 whether they can work in a different way.
86 00;04;14;03 00;04;15;20 The reason for that is this phenomenon
87 00;04;15;22 00;04;18;03 in evolutionary biology that is called exaptation.
88 00;04;18;12 00;04;22;09 And, this is the concept that one biological function
89 00;04;22;11 00;04;24;25 that is materialized through some material entity
90 00;04;25;00 00;04;27;02 that is say, invented by evolution,
91 00;04;27;06 00;04;29;03 may be born with a given function
92 00;04;29;05 00;04;31;08 and eventually maybe recycled
93 00;04;31;09 00;04;33;28 into something very, very different. The typical example
94 00;04;34;02 00;04;37;20 are the feathers in evolution. So, they were invented
95 00;04;37;22 00;04;40;15 to provide a thermal insulation to dinosaurs,
96 00;04;40;17 00;04;44;08 but, the success of feathers was not that one, but
97 00;04;44;11 00;04;48;23 a very different one to provide mechanics for bird flight.
98 00;04;48;25 00;04;51;17 So, you can see in this case, we have multiple examples
99 00;04;51;19 00;04;53;07 in biology from molecular biology
100 00;04;53;09 00;04;56;28 to zoology, and all the rest of it, that are components
101 00;04;57;00 00;04;58;13 of a biological system that have
102 00;04;58;15 00;05;01;23 in one evolutionary stage, one specific function,
103 00;05;01;25 00;05;03;20 might have it completely different.
104 00;05;03;22 00;05;07;04 So, that puts a big barrier on using evolutionary approaches
105 00;05;07;06 00;05;08;27 to understand how things work.
106 00;05;09;05 00;05;11;01 We can understand where they come from
107 00;05;11;02 00;05;12;10 but, how do they work?
108 00;05;12;22 00;05;15;19 Well this is the moment where synthetic biology
109 00;05;15;23 00;05;18;17 really makes its entry in biology.
110 00;05;18;22 00;05;21;00 And, what synthetic biology proposes
111 00;05;21;01 00;05;23;01 is to look at live systems
112 00;05;23;04 00;05;28;02 using engineering as a metaphor, or as an interpretive frame,
113 00;05;28;06 00;05;30;10 to understand, make sense, and eventually
114 00;05;30;11 00;05;32;17 rebuild biological systems.
115 00;05;33;08 00;05;36;19 So, the big novelty in synthetic biology
116 00;05;36;21 00;05;39;05 is that the whole emphasis of the field
117 00;05;39;07 00;05;42;10 is understanding and approaching
118 00;05;42;15 00;05;45;06 the compositional and rational logic
119 00;05;45;08 00;05;47;28 of biological systems, and not so much being concerned
120 00;05;48;00 00;05;49;21 about their evolutionary origin.
121 00;05;49;26 00;05;52;00 And, this is a different perspective
122 00;05;52;01 00;05;53;13 of what has been the traditional
123 00;05;53;17 00;05;56;05 biology thus far. So under this new umbrella
124 00;05;56;07 00;05;58;14 one can approach biological complexity
125 00;05;58;21 00;06;03;18 from the perspective of dividing the system
126 00;06;03;20 00;06;06;23 in various hierarchical levels.
127 00;06;06;26 00;06;09;14 You have the parts, that is the most basic level.
128 00;06;09;16 00;06;12;12 Parts will make devices. Devices will make systems.
129 00;06;12;16 00;06;16;12 In the frame of the abstraction hierarchy, that is so common
130 00;06;16;14 00;06;20;01 in different types of engineering. And then under that umbrella,
131 00;06;20;03 00;06;21;18 under that interpretive frame,
132 00;06;21;20 00;06;24;24 we can replace altogether
133 00;06;24;26 00;06;27;06 the central dogma of molecular biology,
134 00;06;27;07 00;06;28;16 DNA, RNA, proteins,
135 00;06;28;18 00;06;33;27 by an alternative. Or another tenet, that parts make devices,
136 00;06;34;00 00;06;35;04 and devices make systems.
137 00;06;35;06 00;06;38;18 Perhaps with this intermediate stage of models.
138 00;06;38;20 00;06;41;28 So, synthetic biology has not appeared out of the blue
139 00;06;42;00 00;06;45;15 it is rooted in the history of biology, and molecular biology,
140 00;06;45;17 00;06;47;28 but also it has adopted
141 00;06;48;01 00;06;50;25 other sources of knowledge, and elements,
142 00;06;50;27 00;06;52;10 and concepts, and tools,
143 00;06;52;11 00;06;55;21 from other disciplines such as engineering, obviously,
144 00;06;55;23 00;06;59;13 computing, modeling, but also there is a big component about
145 00;06;59;15 00;07;02;16 origin of life, and artificial life, because there is this issue
146 00;07;02;18 00;07;05;19 on, simplifying biological systems to the point
147 00;07;05;21 00;07;07;08 that they can simply work
148 00;07;07;10 00;07;09;24 and this is something that has a great connection
149 00;07;09;27 00;07;12;18 with those that have interest with the origin of life.
150 00;07;12;20 00;07;15;01 So, these are three good various branches biology roots
151 00;07;15;03 00;07;17;23 and you will have the opportunity to
152 00;07;17;24 00;07;19;25 witness various approaches
153 00;07;19;26 00;07;21;10 to the same question
154 00;07;21;12 00;07;22;21 through the various videos that you are going
155 00;07;22;22 00;07;24;02 to see in this series.
156 00;07;24;26 00;07;26;16 So, what is the advantage
157 00;07;26;18 00;07;28;12 of adopting these engineering metaphors?
158 00;07;28;15 00;07;30;15 Well, the advantage is by adopting them
159 00;07;30;19 00;07;32;29 we can see in biological systems
160 00;07;33;01 00;07;35;01 things that have never been seen before.
161 00;07;35;03 00;07;37;24 So, if you show bacteria
162 00;07;37;26 00;07;40;16 to people with different engineering backgrounds,
163 00;07;40;18 00;07;42;15 they may see very, very different things.
164 00;07;42;17 00;07;46;08 A standard biology will see a bacterium. A body with
165 00;07;46;10 00;07;48;28 cells, a membrane, outer membrane, inner membrane.
166 00;07;49;00 00;07;51;01 Well, if you show these to a
167 00;07;51;03 00;07;54;25 electrical engineer, what he, or she, may see instead
168 00;07;54;27 00;07;58;24 is a complex circuit with various components that are
169 00;07;58;26 00;08;00;18 connected in a very particular way.
170 00;08;00;20 00;08;03;19 And because of this connectivity they develop a new function.
171 00;08;03;21 00;08;08;00 And, well by the same token, in radios you have
172 00;08;08;02 00;08;10;29 transistors, connectors, and speakers and so.
173 00;08;11;01 00;08;15;26 One can see a biological systems, for instance bacteria,
174 00;08;15;29 00;08;18;24 also, as a collection of parts that are
175 00;08;18;26 00;08;22;25 connected through a specific plan,
176 00;08;22;27 00;08;24;13 and a specific blueprint.
177 00;08;24;15 00;08;27;21 That will allow you, not only to understand
178 00;08;27;24 00;08;29;23 how the plan is made, but also how to rewire it
179 00;08;29;25 00;08;32;11 to acquire new functionality.
180 00;08;32;13 00;08;34;24 But if you show this same bacteria to a computer scientist,
181 00;08;34;25 00;08;38;03 then they may see, in the very same object,
182 00;08;38;04 00;08;39;19 something different. Like a
183 00;08;39;20 00;08;42;14 computational device, that is able to take inputs
184 00;08;42;17 00;08;44;08 and convert them into outputs.
185 00;08;44;11 00;08;47;03 And this metaphor, this interpretive frame,
186 00;08;47;04 00;08;48;13 has been very useful
187 00;08;48;14 00;08;50;21 in the hands of people, such as Antoine Danchin,
188 00;08;50;23 00;08;54;16 to use that to propose new languages, new methodologies,
189 00;08;54;18 00;08;56;26 and new agenda, in synthetic biology,
190 00;08;56;28 00;09;01;06 by benefiting from this new perspective in looking at things.
191 00;09;01;13 00;09;03;24 But if you show the same cells to a chemical engineer,
192 00;09;03;26 00;09;06;12 what they will see is a fantastic, and super complex,
193 00;09;06;13 00;09;07;13 and very small,
194 00;09;07;14 00;09;10;26 chemical factory. With all the pipes, all the functions,
195 00;09;10;28 00;09;12;19 all the chemicals for the transformations.
196 00;09;12;24 00;09;16;21 So, by adopting and seeing all these metaphors
197 00;09;16;22 00;09;17;29 and these frames
198 00;09;18;00 00;09;20;09 we can really extract a lot of what is going
199 00;09;20;10 00;09;21;14 on in biological systems.
200 00;09;21;16 00;09;23;07 Not only from the point of view of understanding,
201 00;09;23;09 00;09;26;08 but also from the point of doing, and this is
202 00;09;26;10 00;09;28;18 perhaps one of the most exciting challenges
203 00;09;28;19 00;09;30;14 that we face in the field.
204 00;09;30;16 00;09;34;00 To do that, one has to start with a biological system already
205 00;09;34;02 00;09;37;18 like it is. Decompose that into parts, and in many cases
206 00;09;37;20 00;09;40;15 we are helped by the modern technology of omics.
207 00;09;40;17 00;09;42;22 Proteomics, genomics, and all the rest of it.
208 00;09;42;26 00;09;45;20 And then once we have the parts we can produce
209 00;09;45;22 00;09;48;10 a simplified model that will help us to understand
210 00;09;48;12 00;09;50;25 how it is. But, in the case of synthetic biology,
211 00;09;50;27 00;09;53;09 what is the big excitement
212 00;09;53;11 00;09;55;22 is the possibility of using these very same parts
213 00;09;55;24 00;09;58;20 and do objects that are different and do different things.
214 00;09;58;22 00;10;01;18 And, this is precisely what we are now, and what attracts
215 00;10;01;21 00;10;04;04 the attention of the public, and also
216 00;10;04;06 00;10;07;07 of the, say, leaders of opinion.
217 00;10;07;09 00;10;09;17 And, the leaders of our society, because
218 00;10;09;19 00;10;11;28 they see, as we see that ourselves
219 00;10;12;00 00;10;14;13 a tremendous power in the development
220 00;10;14;15 00;10;18;23 of synthetic biology in the future. And, it comes as no surprise
221 00;10;18;25 00;10;20;20 that this type of technologies have been picked
222 00;10;20;22 00;10;22;29 as one of the most promising and transformative
223 00;10;23;01 00;10;25;26 technologies of the future. As you will see in this report
224 00;10;25;28 00;10;28;24 and many others of the like.
225 00;10;29;01 00;10;30;29 Obviously these developments are not devoid
226 00;10;31;00 00;10;33;10 of social consequences, and
227 00;10;33;12 00;10;38;02 as is the case also in many other stages in history, where science
228 00;10;38;04 00;10;40;22 has made a big breakthrough, with transformative potential,
229 00;10;40;24 00;10;42;06 for instance in this picture
230 00;10;42;08 00;10;44;20 you have the invention of anesthetics.
231 00;10;44;23 00;10;49;05 Then it is logical, it is even expected
232 00;10;49;08 00;10;51;07 that society will react to it in various ways
233 00;10;51;09 00;10;53;17 and will raise interesting question. For instance,
234 00;10;53;21 00;10;55;06 what is the science behind it?
235 00;10;55;08 00;10;58;12 Is it safe? What are the risks? How about intellectual property?
236 00;10;58;14 00;11;00;23 Who benefits? Are we playing something
237 00;11;00;26 00;11;02;14 wrong that should be avoided?
238 00;11;02;16 00;11;05;03 Well all these matters are above the table
239 00;11;05;05 00;11;07;25 and have a connection to synthetic biology and they are
240 00;11;07;27 00;11;09;22 entirely legitimate debates that we have to have
241 00;11;09;24 00;11;12;12 to implement the immense potential
242 00;11;12;13 00;11;14;05 that we have in this field.
243 00;11;14;06 00;11;18;26 So, I just want to finish this little introduction to the course,
244 00;11;18;28 00;11;22;11 telling you that one of the magnets of synthetic biology
245 00;11;22;13 00;11;26;06 is to attract to the field to some of the most creative
246 00;11;26;08 00;11;28;25 minds of our time. I have no
247 00;11;28;27 00;11;32;03 misgiving to say that, if Leonardo would live today
248 00;11;32;05 00;11;34;16 he would be a synthetic biologist. Thank you.

This Talk

Speaker: Victor de Lorenzo

Audience:

Educators of H. School / Intro Undergrad
Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: June 2015

Talk Overview

The European Molecular Biology Organization (EMBO)/iBiology synthetic biology course is a series of talks about synthetic biology. It covers general principles, technical challenges, current research, and ethical issues in synthetic biology research. The synthetic biology course is based on the EMBO Synthetic Biology in Action Course, which was held at the European Molecular Biology Lab (EMBL) in Heidelberg, Germany over two weeks in June 2015. In addition to the faculty lectures, there are five videos created by the graduate student and post-doc course participants where they describe and demonstrate the lab portion of the course. Dr. Victor de Lorenzo (Centro Nacional de Biotecnología), Dr. Jacqueline Dreyer-Lamm (EMBL), Dr. Sarah Goodwin (iBiology), and Dr. Ron Vale (iBiology/UCSF/HHMI) were the synthetic biology course directors for this collaboration, and video production was care of the Photolab team at EMBL (Claudiu Grozea, Marietta Schupp, and Doros Panayi) and iBiology (Eric Kornblum). EMBO funded the production of the synthetic biology course.

Speaker Bio

Victor de Lorenzo

Victor de Lorenzo

Although trained as a chemist, Víctor de Lorenzo is now a Professor of Molecular Environmental Microbiology at the Centro Nacional de Biotecnología-CSIC. His lab uses Pseudomonas putida to recreate and build circuits for the sake of new-to-nature biological activities that will have an environmental impact by interacting with chemical waste. Dr. de Lorenzo is a… Continue Reading