Our 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 greatexamples 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-blocks containing more than one quorum sensing systems. Applying multiple quorum sensing systems is not a straightforward thing, We've tested the cross-talk between AHLs and their receiver proteins and choose Las Quorum sensing system from Pseudomonas aeruginosa and Rpa system from Rhodopseudomonas palustris to construct advanced bio-blocks we used for demonstration due to the high orthogonality between them.

Mainly used as intermediate layers carries out logic processing, The Advanced Bio-Blocks often produce a kind of AHLs in response to another. But is a hard task Measuring the actual level of AHLs. We proposed an indirect measurement method for determining the efficiency of Advanced Bio-Blocks.

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.

Team:Shanghaitech/project