What Synthetic Biology Can Do For You

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I give a talk at the Terry Talks 2009.

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  • What do we think of when we hear the word, “bacteria”?
    -Little creatures that live in our gut, in the soil, on our skin... ubiquitous, everywhere.

    Have we thought of them differently?
    -computers?
    -gas guzzlers?
    -energy storage tankers?

    Why can we think of bacteria this way?
  • Well, I’m going to tell everybody about a new and exciting field called “synthetic biology”. However.....
  • ...to understand synthetic biology, we need some conceptual basics. So let’s first understand briefly what the central dogma is.
  • This is the central dogma of biology which virtually all scientists accept as valid. A segment of DNA encodes for a copy of itself, called mRNA, which then gets translated into proteins.

    Benefit of non-biologists: analogy.
  • One thing we often neglect is that the protein has some function. So just as an transit station performs its function in a transit system in allowing people to hop onto trains, proteins perform enzymatic, signaling or structural functions in living systems.
  • Central dogma - general rule of life
  • Functions include stuff more than coding for proteins. For example, there are docking sites for proteins that sense molecules outside of the cell. There are “stop signs” that tell a protein running along the length of the DNA to stop running.
  • So if we think about these chunks of DNA with discrete functions, we can start viewing them as “parts” of a bigger machine... much like lego bricks.
  • So if we think about these chunks of DNA with discrete functions, we can start viewing them as “parts” of a bigger machine... much like lego bricks.
  • Then, we can take these discrete parts, cut them out, and assemble them together into another bigger machine. Let’s go through an example.
  • Let’s take the E. coli docking site for a sugar-sensing protein, join that together with green fluorescent protein from jellyfish along with its variants, and add in the stop sign from yet another bacteria. What can we get?
  • with a bit of an artistic touch, we can easily make this:
  • Underlying all of this, really, is what we call “classical genetic engineering” technology. But here’s where a problem crops up. Scientists have been doing these things using their favorite enzymes and favorite protocols, and so the technology has been around, just not very interoperable.
  • Let’s think about that train station again - what if the station weren’t made from standardized parts? What if the engineers of the 1800s didn’t come together to standardize the thickness, lengths and turns of the nuts and bolts used for building things? I think we can agree that this building would be awfully hard to build.
  • In the same way, we can start thinking about standardizing these DNA parts. Let’s make a standard way of cutting and pasting them together, and add on a standard way of describing each category of parts. And let’s tag on part numbers, so that we can easily know what part we’re talking about.
  • And so with this, we start to build a picture of what synthetic biology is all about. It’s about bringing standardiztion to biology, so we’re not working with bits of knowledge all over the place. What follows from standardization is that we no longer think about the individual parts as ATGCs, we can start abstracting them into their functions, much like computer programmers don’t think about 0s and 1s but instead use object-oriented principles for designing their programs. We also get into this era of enabling the custom-design of DNA parts using automated DNA synthesis technology, which lets us write DNA the way we want it.
  • So this is starting to look like programming, isn’t it? We write a genetic program, and stick it inside a cell, which becomes our platform...
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • That’s just like Microsoft writing programs for windows, Apple writing the awesome iWork 09 suite for Macs... in the same way, we could potentially write really exciting genetic programs for various life platforms.
  • Thus, we’ve built a picture of what synthetic biology is about. It’s about the standardization of the process of genetic engineering, and doing this on a few broadly accepted platforms.
  • The consequence of this is that biotechnology is now way more accessible.
  • with a bit of an artistic touch, you can make this:
  • And that the standardization process helps enable the development of new applications. Let’s look at two genetic programs as examples.
  • So if you think about it, this technology can impact the world. We can start to think about even more applications.
  • We can program bacteria to behave like homing missiles to selectively target cancer cells and destroy them.
  • We can reprogram E. coli to consume greenhouse gases out of the atmosphere, and perhaps even spit back out useful chemical or pharmaceutical products while at it.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • Think about the genetic oscillator and the possibilities - we can start designing synthetic gene networks that enable counting and thus biological computation.
  • The sky is the limit. Because of the potential applications, synthetic biology is absolutely exciting.
  • I’ve shown you all how synthetic biology is really an interdisciplinary field, bringing biology, engineering, math, and chemistry together. The industry is taking an interest in this field as well. Moreover, informed discussions can shape how we take responsible stewardship for this technology.
  • Synthetic biology is fundamentally very powerful, and with this power comes responsibility. How would we utilize this technology for the benefit of mankind? How do we best manage the resources available to synthetic biologists?

    It also raises another question - how do we approach teaching the life sciences?
  • Here at UBC, there is a defect in the way we are taught in the life sciences departments, and synthetic biology offers an opportunity to change the way we think about life science education. Here at UBC, our faculty have engaged our intellect brilliantly, but sadly enough, the curriculum neglects practical learning.
  • Would you rather learn established facts, or sit in on a lecture? Would you rather learn by tackling a problem or even designing and carrying out an experiment?

    I contend that if we harness the talents of undergraduates by not only connecting with our minds, but also engaging our hands, then, by adopting this learning philosophy............
  • Now, you may wonder where that learning philosophy came from?
  • There’s a learning philosophy that I really like, called ‘Mens et Manus’, and it came out of one of the top research universities in the world - the Massachussetts Institute of Technology. It’s a place that I really want to go to. Mens et manus means that the institute seeks to engage both the minds and the hands of their students. Not only knowing knowledge and how to think, but also knowing how to do.
  • It’s here that people realized that not only can people with PhDs contribute significantly to practical research, but also undergraduates like myself!
  • It’s here that people realized that not only can people with PhDs contribute significantly to practical research, but also undergraduates like myself!
  • Out of this empowering and engaging educational philosophy came the International Genetically Engineered Machines competition, also known as iGEM, which is the premier international undergraduate research competition in synthetic biology.
  • This year, UBC has a team too! We have many people who came together to form this team, but none more foundational than Dr. Eric Lagally from the Michael Smith Laboratories.
  • By sponsoring the formation of an iGEM team at UBC, he has brought to us the complete research experience.
  • We came up with our own idea, to build an analog biosensor with thresholds for outputs. It’s almost like building an E. coli traffic light that produces a different fluorescent protein in response to different concentrations of arabinose. If we swapped out the arabinose sensor for a pollutant sensor, and the fluorescent proteins for pollutant-degrading enzymes, then we’d have a really powerful environmental-protection biomachine!
  • There’s more too!
  • Here’s just a subset of the sponsors for our team this year...
    I remember writing with the team the grant proposal requested of us by the CIHR-MSFHR Training Program in Transplantation, as well as working with Dr. Lagally and the team on the proposal to UBC’s TLEF. In our regular undergraduate research environment, we hardly ever get to do this.
  • There’s the experiments too!
  • I remember designing and conducting experiments collaboratively with my teammates, pulling 12, 13 and 14 hour days just to get assemblies and data to put together. The constant frustrations, the occasional success... typical lab life...
  • And now, we’re in the process of writing up and documenting our work for the rest of the world to see, before we fly off to the Jamboree at the end of October.
  • And so this is really a model of how we should be teaching the life sciences - ...
  • We can program bacteria to behave like homing missiles to selectively target cancer cells and destroy them.
  • Applied & problem-based. Mens et manus, where we engage our minds and our hands to think of solutions for bigger problems. This is an opportunity to get UBC to start thinking about teaching the way MIT does, and start producing life science graduates who aren’t just supplying the BC workforce with labor, but rather, going out and innovating and solving world problems using biotechnology.
  • I’d like to stronlgy encourage everybody to check out the UBC iGEM booth just outside during the break to learn from us about how YOU can get involved with this really exciting learning journey. Thank you!
  • What Synthetic Biology Can Do For You

    1. 1. Let’s think about bacteria...
    2. 2. Synthetic biology
    3. 3. Let’s talk about Biology’s Central Dogma
    4. 4. DNA mRNA Protein Function Function Function Transit Vancouver Halifax Station
    5. 5. General Rule: DNA mRNA Protein Function
    6. 6. Let’s break a rule DNA mRNA have function All DNA Protein Function sensing protein coding tln initiation stop signs Images courtesy of Parts Registry (parts.mit.edu)
    7. 7. Think of these as DNA parts Images courtesy of Parts Registry (parts.mit.edu)
    8. 8. Think of these as DNA parts Images courtesy of Parts Registry (parts.mit.edu)
    9. 9. We can put these parts together, and stick them into bacteria Parts of DNA
    10. 10. Escherichia Aequorea coli Vibrio victoria arabinose- fischeri GFP & sensing terminator variants promoter + + = ??
    11. 11. Images courtesy of Roger Tsien Lab (http://www.tsienlab.ucsd.edu/Images.htm)
    12. 12. Reading DNA Genetic Engineering Cutting & Pasting DNA
    13. 13. Let’s standardized these parts BBa_J23100 BBa_K145015 BBa_B0034 BBa_B0014 Images courtesy of Parts Registry (parts.mit.edu)
    14. 14. Writing DNA Synthetic Abstraction & Design Biology Standardization Reading DNA Genetic Engineering Cutting & Pasting DNA
    15. 15. Assembling DNA is like programming! Genetic Programs this is the platform
    16. 16. so-so??
    17. 17. awesome! so-so??
    18. 18. really exciting! Genetic Programs awesome! so-so??
    19. 19. Platform Writing DNA Synthetic Abstraction & Design Biology Standardization Reading DNA Genetic Engineering Cutting & Pasting DNA
    20. 20. Synthetic biology makes biotechnology accessible
    21. 21. Standardization enables development
    22. 22. Biochemical Bags of Blood + + + + Oxygen Protein Freeze- transport production drying controller Immunologically Genetic invisible chassis self-destruct Images courtesy of UC Berkeley’s 2007 iGEM Team (http://parts.mit.edu/igem07/index.php/ Berkeley_UC)
    23. 23. Genetic Oscillators Video taken from Stricker et. al.; Nature 2008 vol. 456, 516-519; doi:10.1038/nature07389
    24. 24. Genetic Oscillators Video taken from Stricker et. al.; Nature 2008 vol. 456, 516-519; doi:10.1038/nature07389
    25. 25. Genetic programming using Synthetic Biology can impact the WORLD!
    26. 26. “Gas-Guzzling” bacteria can consume greenhouse gases
    27. 27. We can do biological computation
    28. 28. We can do biological computation 1 A 2 B 3 C Friedland et. al., Science 2009
    29. 29. We can do biological computation 1 A 2 B 001011001001 3 C Friedland et. al., Science Sometime coming...? 2009
    30. 30. Synthetic biology is exciting!
    31. 31. Synthetic biology is exciting!
    32. 32. interdisciplinary
    33. 33. fundamentally powerful
    34. 34. Synthetic biology can change the way we think about life science education
    35. 35. Mens et Manus ::: Mind and Hand
    36. 36. www.igem.org
    37. 37. 2009!
    38. 38. Th La kan ga s D lly r !!! . 2009!
    39. 39. idea complete writeup research funding experience experiments
    40. 40. idea Analog biosensor with increasing arabinose thresholds for outputs Applications in biomedical diagnostics, therapeutics & environmental sensing
    41. 41. idea complete writeup research funding experience experiments
    42. 42. funding UBC Teaching & Learning Enhancement Fund
    43. 43. idea complete writeup research funding experience experiments
    44. 44. experiments
    45. 45. idea complete writeup research funding experience experiments
    46. 46. writeup
    47. 47. idea complete writeup research funding experience experiments
    48. 48. We can finally move into an era of applied & problem-based learning
    49. 49. www.igem.org www.ubcigem.com

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