Distributed Computation in Synthetic Cellular Consortia

Final Report Summary - SYNCOM (Distributed Computation in Synthetic Cellular Consortia)

Engineered synthetic biological devices have been designed to perform a variety of functions, from sensing and bioremediation to energy production and biomedical applications. However, there is not a standardized way to build and engineer synthetic biological circuits. One of the major limitations to build biological circuits is how to connect the different elements that are part of a circuit. In electronics, circuits are made by connecting different modules through wires. However, inside of a cell the modules are not spatially isolated and the wiring is implemented by wiring molecules that need to be specific and prevent crosstalk to ensure good circuit performance. This is a challenge, since the more complex the circuit the more wiring molecules are needed raising the complexity of building the circuit and having problems of scalability. Thus, the future success of complex synthetic biological devices will depend on obtaining standardized circuits that are easy to scale up and preferably allow for the reuse of some parts to simplify the building process. Here, we have shown that complex computational devices can be obtained by using a different logic and space as a key computational elements in multicellular consortia with distributed computation. This new approach uses a general architecture that is independent of the circuit’s complexity and involves minimal genetic engineering and permit to reuse parts to build new circuits without further genetic engineering. This approach grants scalability and allows the development of complex circuits while reducing cell engineering. To do this we engineered a minimal cell library with cells that respond to the input in a simple ID/NOT logic gate and produce a wiring molecule that another cell process with a NOT logic to produce the output of the circuit. These cells are spatially distributed in different chambers forming a modular biocomputer, and the different outputs of the chambers are collected together to generate the final output of the circuit. This architecture is not only flexible, robust and scalable, but also, it allows building complex logic functions that can be reprogrammed. This design was implemented in yeast but can be transferred to any organism. Because one key element of this architecture is the spatial segregation of the different elements of the computation, and thus this can be explored using custom microfluidic devices. We have been working with 3D printing technologies to build custom microfluidic devices that will allow for easy and modular building of the chip as well as it allows for fast dissemination of the technology at reduced cost. We have also shown that by a minimal genetic engineering we can build memory circuits that can retain 1-bit of memory. This was achieved by co-culturing 2 populations that produce and secretes different wiring molecules that inhibit each other. These results suggest that our approach is as valid to build combinatorial circuits as for build-ing circuits with memory and potential sequential circuits in the future. While these results are interesting we believe that our work could be improved by further reducing the wiring molecules from one to none and building a wireless multicellular circuit or by making a more standardized circuit that can be reprogrammed to performed different logic gates.

Final Report Summary - SYNCOM (Distributed Computation in Synthetic Cellular Consortia)

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