Team:Shanghaitech/project
Huge Gap between the public & synthetic biology
Public participation is a powerful booster for science advancement. The game, FoldIT, had encouraged thousands of people contribute to the structural biology research using their three-dimensional pattern matching and spatial-temporal reasoning ability. Folding@Home, another protein folding program based on public participation, had accumulated the computing efficiency that overrun all other super-computers during 2007-2012.
We image a future of synthetic biology like this, when people in different field can contribute their intelligence to advance synthetic biology. However, it is not easy for non-biologists to start working on gene blocks since it requires a complex understanding of molecular cloning, sufficient biosafety training as well as an actual lab. In this project, we tried to build a public platform for synthetic biology with two attempts.
First, we simplified the “block” concept to the public.Instead of using gene blocks, we consider a group of functionally definedbacteria as a “block”. Quorum sensing (QS) system in synthetic biology is great examples to show that bacteria cells can communicate to achieve differentfunction. Thus, we use QS system as the executioners to achieve synthetic aim inour project.
Secondly, we built an interactive platform that combinessoftware control with an automatic liquid handling system. With this platform,most people, even elementary school students, can design their syntheticbiology experiment online and have the robot perform their experiments.
Pack the difficulties in the box: how can our project narrow the gap
We aim to build a platform named MagicBlock, consisting of an interactive software interface, bacteria and robots. Designers can use the software interface to design gene circuits of a bio-product. Several MagicBlocks, the bacteria, are cultured according to the gene circuits retrieved from the cloud server and these blocks are interacted by liquid handling robot for supernatant transfer.
What’s Lux-like Quorum Sensing system?
In Gram Negative bacteria, Acyl Homoserine Lactones (AHLs) are used to communicate among their community. A family of AHL-synthetases keep synthesize AHLs in a relative low level. When the bacteria population increases and the synthesized AHLs reach a critical concentration, AHLs bind and induce the dimerization of LuxR-like receiver proteins, which in turn allow the protein to bind specific promoters to initiate gene expression. We've used this feature of communicating between bacteria to connect our MagicBlocks together.
"Primary Bio-Blocks" are Bio-Blocks containing single quorum sensing system.
We've named simple Bio-Blocks containing only one quorumsensing system "Primary Bio-Blocks". These simple bio-blocks are mainly used as input/output (I/O) units, response to physical or chemicalstimulations, send input signals to the whole MagicBlock system, or express highlevel of a reporter protein as the output.
We generated a collection of these bacteria sensors andreporters. Since they are sharing the similar design, one can easily switchbetween these bio-blocks to change the function for different purpose.
To validate thefunction of these primary bio-blocks, experimental tests have been combinedwith mathematic modeling to better characterize each QS system.
"Advanced Bio-Blocks" are Bio-Blocks containing more than one quorum sensing systems.
"Advanced Bio-Blocks" refer to bio-blockscontaining more than one quorum sensing systems. Applying multiple quorumsensing systems is not a straightforward thing. We've examined the cross-talkbetween AHLs and their receiver proteins. Las quorum sensing system from Pseudomonas aeruginosa and Rpa systemfrom Rhodopseudomonas palustris demonstrated great orthogonal function in our experiments, thus we used them to construct theadvanced bio-blocks.
Mainly used as the intermediatelayers carrying out logic processing, the Advanced Bio-Blocks often produce onekind of AHLs in response to another. However, it is hard to measure the actuallevel of each AHL. We have generated an indirect method to determine theefficiency of Advanced Bio-Blocks by mathematic modelling.
Dynamical model of a typical bio-block
Indicate the main factor affecting the growth of E.coli from both theoretical simulation and experiment.
Automated devices helps to realize bio-block concept.
Figure: How the whole system works?
Automated devices are used to transfer culture supernatant and connect different MagicBlocks together. Users could design genetic circuits through our software with easy to use user interface, then their design will automatically be translated as machine code controlling the robotic liquid handling system, transferring supernatant between bacteria cultures and connecting bio-blocks.
Hardware
Common liquid handling robots are far too expensive for a project aiming at public engagement. We've built a Low-cost Robotic Liquid handling system to assemble our MagicBlocks. For a cost of only $150, our improvise liquid handling robot had been proved competent to complete the task of assembling Bio-Blocks.
Figure: Low-cost Robotic liquid handling system.
Software
Our controlling software is one of the essential parts to allow people to design a synthetic gene circuit. We've created an user-friendly software for this purpose. Anyone could use it to assemble MagicBlocks with the function of their desire, but no need for any wet-lab training.
Human Practice in our project
In the Human Practice part, we found the problem,designed a product, tested it and received evaluation.
After interviewing people at different ages and withdifferent occupations, we encountered many person with fascinating ideas, yethave little biological knowledge or lab experience. Hence we invented MagicBlock, an integrated platform for users to design and modify theirbio-product simply by programming. The public were invited to the workshops,where they were guided to use MagicBlock to design their own bio-products andcreated various thought-provoking designs. We got feedback and improved theMagicBlock accordingly. In the end, it is rewarding to find out that ourMagicBlock can really inspire people’s creativity and help them to realize it.
We’ve also got experts’ opinions by interviewing, seeking advices on building the MagicBlockas well as the related mathematic modeling.
