Intro Episode - Transcript

Tess (T): Synversations a podcast that explores the depth of synthetic biology from various multi-disciplinary standpoints. I'm Tess King your host for today. I'm a third year student here at the University of Toronto studying physics and physical geography. Synversations is a five episode long podcast created by the University of Toronto policy and practices division of its iGEM, team a student club dedicated to synthetic biology. For first episode will be unfolding the history of synthetic biology and delving into the definition of what synthetic biology really is and its importance. Also, joining us today are Victoria our wet lab lead.

Victoria (V): Hi my name is Victoria Sajtovich and I am the research and development Wet lab Lead for the iGEM team.

T: Ali, the Dry Lab Lead. 

Ali (A): My name is Ali and I’m the Lead for the Dry Lab. I am currently studying statistics and fundamental mental genetics and its applications. 

Estee (E): Hi I’m, Estée and I’m the Policy and Practices Lead. Third year Ethics, Society and Law and Bioethics Major. And I’m the resident biology novice today and I'll be asking questions when I don't understand something.

T: Now for some context into synthetic biology and its development. The origins of synthetic biology can be traced back to 1828 Frederich Wöhler a German chemist applied ammonium chloride to silver isocyanate to produce urea, a substance that’s found in urine. Later on in the 1970s this field gradually advanced when scientists conduct experiments in genetic engineering and recombinant DNA technology. In other words scientists modified the genetic code of a naturally occurring back to your to alter their function. This gave rise to the production of biological drugs such as insulin a hormone created by the pancreas that helps break down sugar in your body. Following the rise of genetic engineering in the early 2000s researchers found ways to create customized genes which were rebuilt from scratch. Using these customized stretches of DNA. Scientists have been creating organic compounds are tailored towards specific needs, for instance artemisinin and anti-malarial drug that is produced from the naturally occurring warm wood plant by using the techniques synthetic biology the scientists combined the DNA sequences the planet with that of yeast and bacteria to increase the production of Artemisinin. Now to segue into our interview part. So Ali, what's your definition of synthetic biology?

A: My definition for synthetic biology is the engineering of cellular systems and their components so genetics and proteins. 

T: So, could you explain for the biologically challenged audiences, like myself, what genetics and proteins and all this stuff is. 

A: So, genetics refers to the DNA and the DNA is essentially the instruction manual and the proteins are the tools that are used to build them. So, like let's say you were going to build a bookshelf, the instruction manual would be the DNA and the tools would be the protein. 

V: My personal definition of synthetic biology is it is a discipline of science that’s all about creation. It really focuses on these universal design principles whereby techniques or understanding from the realms of physics engineering mathematics all comes together to try to nail down the principles of life. So, in contrast to say molecular biology where you're trying to understand the fundamental function of a particular gene and how it works in the system as an entire whole in synthetic biology you're taking your knowledge of the entire realm and then using that to create something that's novel. 

T: What are you guys doing?

V: Ok so our project this summer is trying to figure out a mechanism by which we can control the CRISPR – Cas 9 System. It’s currently a huge interest in medicine because there's a lot of diseases that have a genetic basis such as cystic fibrosis that you really want to eliminate and Gene editing is one way by which we could possibly do this. The only problem with that causes is that is all the kinks of it have not been completely worked out because we don't have a complete understanding of it yet to really into the clinic. And one of the problems with it is difficult to control exactly when this Cas 9 endonuclease makes a cut. So what our project is trying to do this summer is to create some way of controlling the CRISPR Cas 9 system and basically turning it on or off at will. So what we've done is actually put the CRISPR system under the control of a protein that responds to light so you can basically shine light on the system and turn it on. And then in order to the CRISPR system off you have something called an Anti-Crispr for proteins which just like the name implies it basically binds to this entire assembly of molecular factors and aggregates its activity. So we've essentially devised a genetic switch for turning CRISPR on and off and we’re looking to implement that this summer. 

E: What is CRISPR?

[00:05:19] OK so the CRISPR – Cas 9 system actually refers to the innate analysis and actually refers to the innate immune system of bacteria. So what this is it is designed to do is identify foreign invaders bacteria as essentially viruses that attack bacteria. So what this system actually stands for is clustered regularly interspace short palindromic repeats what that essentially refers to is a region of DNA in which there are these repeated sections that are interspaced by these sequences of DNA that match viruses that previously infected this bacteria. So what that allows bacteria to do upon a new infection is basically take the sequences transcribe them RNAs. 

E: What is RNA exactly? 

V: RNA is basically like a ribonucleic acid it's the intermediate step between DNA and protein. It’s kind of referred to as the central dogma of molecular biology. Everything -information flows from DNA and RNA to protein, so it’s like an intermediate step. So, this intermediate step basically couples to a protein which is referred to as Cas 9. And then it searches along the bacterial genome looking for a similar sequence to that process. So what scientists have basically figured out how to do is to synthetically alter that CRISPR RNA into a single guide RNA which just means it all one molecule and then it can find any other sequence in the genome similar to the search function in a word processor. So it's almost as if you can find any set of letters in the entire genome to find a very specific location.

E: What would you use for it?

V: So as I was explaining previously scientists have found a way to basically modify the SGRNA which is like the search function. So scientists can actually go and locate any gene in the entire genome. And then because the Cas 9 is called it and a nucleus which means it basically has the ability to create double strand breaks the DNA you can go in and cut a sequence of DNA and then you can insert exogenous sequences. 

E: What does exogenous mean?

V: like a DNA sequence that comes from another source. It's not it's common to the organism. So when one of the broader themes in synthetic biology as a whole because the DNA code is actually universal, everybody has ATC and G in their genome.

E: Everybody?

V: Everybody it just refers to four different nucleotides in different sequences create different chemical messages and those messages are basically read by a variety of other chemical messages in your body to create, to express whatever these things are say which is in terms of proteins. So basically The long and the short of the CRISPR-Cas9 is we can go find any gene cut it and insert new DNA. 

E: Why would we want to do that? 

V: For a variety of reasons, that’s getting to why we have I think biology in the first place. So now that we better understand these biological principles we can go in and basically use organisms to do any sort of function. So say you have a plant and you know the global food crisis is a major issue right now and you want to increase the focus in the past. So it's more productive and you have higher yield. So we can go in and try to alter these metabolic pathways with genes from other organisms to basically create something that will aid human society. 

T: So what is a Dry Lab trial generally. 

A: So a Dry lab is basically using computational and mathematical models on biological concepts. When you have your wet lab you have people in white lab coats doing transformations collecting the data. That data is then transferred to dry lab and they basically analyze it and develop theoretical models to explain why that data came about. 

T: So are you in a lab with petri dishes and pipettes?

A: no no, we’re usually just sitting at home or in a little room with laptops coding pretty much or doing research. 

T: So what type of software are you using or methods in which you are implementing the work in Dry lab? 

A: So Math Works provided iGEM Teams with a free package for Matlab and simbiology. Which we are going to be using to model the system like I said before. So 

[00:09:54] And like I said before basically what it allows us to do is set up a system computationally to matching different proteins different genes with their enzymes dynamics and that's creating a theoretical mathematical model that's already being well established by medical research. And we're just going to run that. And it will give us an output file which will give us the data for how our system works. So it will be the dynamics between CRISPR and antiCRISPR verses our activation with the light system. And once we understand that we're going to utilize the optimization tool also presented in MATlab which is given to us through Math Works. 

T: Could you explain what Matlab is or what it is a mathematical software package?  Is PC programming language they designed for me to handle me. 

A: MATlab is a mathematical software package, it’s basically programming language that is designed fully to handle matrices, calculus all that stuff you need to apply mathematics to the real world.

T: So what do you think is one of the most important discoveries of synthetic biology. 

A: I think actually one of the most important discoveries was actually before synthetic biology was a thing. I believe that it was the discovery of the double helix structure by Rosalind Franklin because not only was it the basis for everything in biology. It's also a story that has a lot of meat to it and it's just like a lot of drama behind the whole. 

T: Rosalind Franklin? Wasn’t it Crick and Watson who discovered the double helix? 

A: Yeah, they kind of stole it. They were all doing research on it but Rosalind Franklin is the one who actually used crystallography to determine the structure and figured out how to see DNA. Once she finally shared it with one of them they kind of just took it and they both got credit for it. That's why it’s called the Watson Crick model and not the Watson Crick Franklin model. It’s a sad story cause she obviously didn’t get credit for it and actually got sick from the radiation and on top of that she didn’t get her Nobel Prize because she got sick before it was given to her.

T: Wow those guys are massive snakes. All right. So where do you see the technological advances of synthetic biology taking us?

A: I feel like technological advances of synthetic biology will take us in a similar way that computers did. Essentially. I believe that it's going to get so complex that we're eventually going to be able to develop new proteins new systems new organisms to fit our very very basic needs. So for example we already have those seedless tomatoes we have something called golden rice which is basically rice but its just jam packed with nutrients. It's obviously not natural right but it's extremely good for your health. And I think we're going to essentially go one step further. Where are already developing crops to withstand harsh environments and we’re going to make featherless chickens which I personally find very disturbing. 

T: That’s a little disturbing but alright.

A: Yes, they’re freaky right but it's very interesting, basically it’s going to be used to make the everyman’s day or life a lot easier. 

T: What was your motivation for joining the U of T iGEM team. 

A: So I actually heard about iGEM way back in high school I watched a documentary on all those like oh yeah I want to do this and it seems very interesting however when I got to first year I sat in that club room and I was like OK everyone's way too smart for me. I'm just like a first year I'm not going to do it. And a couple years later when I got more knowledge I discovered bioinformatics and I figured I really want to do this aspect of it because I love math, statistics and the application of it in genetics and systems biology is just so fascinating to me so I applied and I somehow got in and that's how I got into iGEM. 

V: I've basically been absolutely obsessed with CRISPR-Cas9 system. And I was looking for a club that was focusing on these new and upcoming applications of biology. I have a little bit of a lab experience I've always wanted to work in a lab my entire life. And I feel like iGEM is the perfect place to acquire the experience of running a project and hopefully moving synthetic biology forward albeit in a very small. 

A: Yeah I going into synthetic biology a long time ago when I first watched Jurassic Park in they extracted DNA from mosquitoes in reverse engineered the dinosaurs. That's kind of like what I wanted to do growing up so I was like OK I'll say biology and you know eventually hopefully when I get like my Ph.D this is the thing I'll do I will create Jurassic Park. I’ll become like a multimillionaire you know so I’ll have my own biotech company and just make dinosaurs for like the everyday kid. 

V: Personally, I'm going to add that I don't think that would be possible. The current state of that synthetic biology is in, however yeah dream big. 

A: Ok like, we put a man on the moon, I'm pretty sure we can do this too. You know we thought that was impossible. They told the Wright Brothers that was impossible I'm sure like 10 years from now we have chickens like giant featherless chickens we’re gonna start making dinosaurs.

V: You know fair point but the practicality of that. And don't you think there's more important problems in medicine and with respect to the environment right now. 

A: You know that like it makes sense but you can't just pour like we are already paying billions of dollars into these problems and are not being solved any faster. There's like so much money in the world you've got you've got NBA players making hundreds of millions of dollars. That's not a big problem. Some people can’t watch basketball but like we do it anyway there are some things that are more important than just solving world problems. You know it's about advancing humanity in some other ways.

V: I fundamentally disagree with that. I definitely agree with you that it is essential for humanity to have some things that are just fascinating and fun, and that's part of human creativity.  But I think that's why the technology has such a great will because you're using that creativity in a way that is actually going to push us forward and just solve those problems because if you focus on generating the dinosaurs then, then it becomes a sort of farcical discipline and any sort of attempt for dreamers where we need to show people that there are real things that we can do and overcome various ethical issues first.

A: Farcical? 

V: Farcical.

A: What does that even mean?

V: Something that’s – 

A: She’s using words she doesn’t even know what they mean/

V: No I do know what it means, a farce is some sort of amusing story or front or joke. 

A: Listen as technology advances the more farcical it becomes, right? Like look we have so much technology when it comes to computers like 30 years ago computers were the size of this entire room probably bigger. No one could afford it, no one could use it. Now we use computers to play videogames they can be using it to solve problem and cancer research but they don't. People develop videogames all the time and console is just a fancy computer. So as technology gets more advanced there's going to be like things that we are going to be doing with it that's frivolous right. 
As more people as it get it, as it becomes more accessible like the same thing with synthetic biology. 
V: Yeah. 

A: Yeah, it's not going to just be right now just for research but it can be commercialized it's going to be for everything. 

V: No I definitely agree that those applications are inevitable. Like I said – 

A: -But you don’t like it. 

V: I think that there's just better things that we could be investing our time in. 

A: Like when you're seven billion people in the world you let some people have some fun. There are people like you know do their thing. 

V: There's a limit. That’s all I’ll say.

A: Ok.

T: Thank you both Ali and Victoria for your insightful input into the development and definition in the field of synthetic biology. Thank you Estée for being our resident biology novice. 

E: Oh my pleasure I had fun.

T: That concludes our first segment of our five episode length podcast Syntalks. Don't forget to check us out on Facebook Instagram and Twitter at iGEMToronto. We'll see you next time with our episode on the cross-section of ethics and synthetic biology.