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Special Session 4: Adam Arkin on Synthetic Biology (ISMB 2009)

Running the Net: Finding and Employing the OPerating Principles of Cellular Systems
Adam Arkin
Part of the Advances and Challenges in Computational Biology, hosted by PLoS Computational Biology

The need for scientific standards and cooperation. Very much data driven in synthetic biology. We’ve been genetic engineering since the dawn of agriculture (teosinte, cows etc). And with dogs, which started around 10,000 years ago. Then the extremely different breeds we have today. That such differences would cause survival effects in the “wild” doesn’t bother many people. Next is the classic example of the cane toad, which destroyed environmental diversity.

Synthetic biology is dedicated to making the engineering of new complex functionsin cells vastly more transparent, and that openness is a really important part. It is trying to find solutions to problems in health, energy, environment, and security.

How can we reduce the time and improve the reliability of biosynthesis? Engineering is all about well-characterized, standard parts and devices. You need standards in parts, protocols, repositories, registries, publications, data and metadata. This helps a lot when you have groups and need to perform coordinated sciences: linux is an example of this working. But is design scalable? While applications will always have application-specific parts, there are sets of functions common or probable in all applications.

You can have structures that regulate most parts of gene expression. In talking about probability of elongation, they use an antisense-RNA-mediated transcription attenuator, which has a recognition motif, a possible terminator, and a coding sequence. Through a series of steps, if a antisense RNA absent, then you get transcription (and the opposite is true too): this is a NOT gate. For transcriptional attenuators, it is possible to design orthogonal mutant lock-key mechanisms. You can obtain orthogonal pairs by rational design but there is a certain attenuation loss. They can’t explain everything about the functioning of these devices. Want to improve communication in this respect. If you put two attenuators on the same transcript, it behaves about as you expect: a NOT-OR gate.

Bacteria engineered as pathogens to target particular human tissue (e.g. tumors). To do that, you have to build many different modules with its own computational and culure unit tests. These different modules/models can be re-used, e.g. in the iGEM competition. The problem is that the complexity of the engineering problem is greatly increased beyond that found in chemical production / bioreactors.

Absolute requirements: openness, transparency, standards, team-science approaches.

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Please note that this post is merely my notes on the presentation. They are not guaranteed to be correct, and unless explicitly stated are not my opinions. They do not reflect the opinions of my employers. Any errors you can happily assume to be mine and no-one else’s. I’m happy to correct any errors you may spot – just let me know!

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Congratulations to the Newcastle Uni iGEM Team 2008!

Congratulations, Bug Busters! You didn't just get a gold star, you got a gold award!

Though I was not involved, many of my friends were part of the Newcastle University iGEM 2008 team, either as supervisors or students. You can read more on the Newcastle University iGEM entry wiki page. Of the 84
teams competing, only 16 won gold medals, including, from the UK, Edinburgh,
Imperial and Newcastle.

From the overview of the team's wiki page:

"We aimed to develop a diagnostic biosensor for detecting pathogens.
We wanted this to be cheaply and readily available for deployment in
areas where access to medical resources, such as refrigeration and
sophisticated laboratories, is limited or absent. We chose to use Bacillus subtilis
as a method of delivery due to its ability to sporulate. The sensor
bacteria could then be dried down as spores, which are very stable and
extremely resilient to hostile environmental conditions, and rehydrated
when required. The ambient temperature of much of the developing world
is ideal for the growth of
Bacillus spp. without the use of incubation equipment.

Gram-positive bacteria communicate using quorum communication
peptides. Research has shown that these peptides are extremely
strain-specific. We chose to engineer
B. subtilis 168 to detect
four Gram-positive pathogens by their quorum communication peptides.
The different combinations of quorum communication peptides would be
sensed by the engineered bacterium, and this signal converted into a
visual output as fluorescent proteins such as mCherry, GFP, CFP and
YFP."
Read more.

Well done!

P.S. Looks like kudos to my old alma mater, Rice University, too! Congrats!

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