Engineering multicellular biocircuits: programming cell-cell communication using plasmids as wires
Date du début: 1 oct. 2013,
Date de fin: 30 sept. 2016
Conjugation is a natural communication mechanism used by plasmids (autonomous self- replicating DNA molecules) to travel from bacteria to bacteria as a survival strategy. The genes and proteins that control conjugation are well known by biologists. This conjugation hardware is highly specific and robust and has been refined over millions of years of natural selection. It allows the independent transmission of different conjugative plasmids without interference even when the plasmids share the same sender or receiver bacteria.We will harness this sophisticated and exquisite biological hardware to engineer a new multicellular communication technology where plasmids will be used as intercellular wires. Among others, during PLASWIRES project we will engineer large multicellular circuits such as a multi-layered AND gate circuit with 5 inputs, or an AND-OR and OR-AND Boolean logic circuit with up to 6 inputs.To simplify the design and implementation of conjugation based circuits we will engineer a multicellular programmable logic array (PLA). To show the power of this cell-cell communication technology, we will solve an NP-complete problem in-vivo: the SAT problem. To solve this problem is interesting not only theoretically, but also in practice: our plasmids solving SAT can potentially be used as programmable antibiotics or sentinel plasmids able to detect danger sets of plasmids in virulent bacteria. PLASWIRES will also develop software (CellModeller and BactoSIM will be the simulators used) to help biologists in the design of all these multicellular circuits.PLASWIRES' ultimate goal is to establish conjugation as a new tool in synthetic biology, which has not previously been exploited, to engineer multicellular circuits with potential applications in biomedicine and biotechnology. From a computational standpoint, PLASWIRES aims to demonstrate that conjugative plasmids are programmable wires enabling distributed bacterial computations. In other words: PLASWIRES' main goal is to show how to program a parallel distributed living computer using conjugative plasmids as wires between cellular processors.
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