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Biological Cells as Computer Logic Units

Synthetic biology is an interdisciplinary branch of biology and engineering. It is used to build artificial biological systems for research purposes and medical applications especially drug development cycles. These synthetic biologists work to convert biological cells into living devices that can perform a variety of tasks. Thus, they combine biological environments with computational machinery that can sense different stimuli.

 

[Video: https://www.youtube.com/watch?v=rD5uNAMbDaQ ]

 

These living devices are similar to electronic circuits, these circuits can be designed to perform a different Boolean logic function, such as AND gates and OR gates. Using those kinds of gates, circuits can detect multiple inputs. A recent publication in nature (doi:10.1038/nature23271) reported that a research group at Harvard's Wyss Institute for Biologically Inspired Engineering reports an all-in-one solution that imbues a molecule of 'ribo'nucleic acid or RNA with the capacity to sense multiple signals and make logical decisions to control protein production with high precision. The study's approach resulted in a genetically encodable RNA nano-device that can perform an unprecedented 12-input logic operation to accurately regulate the expression of a fluorescent reporter protein in E. coli bacteria only when encountering a complex, user-prescribed profile of intra-cellular stimuli. This achievement shall help researchers to construct more sophisticated living circuits; thus taking a further step into the complex cellular environments.

 

"We demonstrate that an RNA molecule can be engineered into a programmable and logically acting "Ribocomputing Device," said Wyss Institute Core Faculty member Peng Yin, Ph.D., who led the study and is also Professor of Systems Biology at Harvard Medical School. "This breakthrough at the interface of nanotechnology and synthetic biology will enable us to design more reliable synthetic biological circuits that are much more conscious of the influences in their environment relevant to specific goals."

 

This is not the first breakthrough for this group in that field, in 2014 they managed to program hair pin-like nanostructures made of RNA “Toehold Switches”. RNA toehold switches control the production of proteins: when a desired complementary 'trigger' RNA binds to the toehold switch, the hairpin structure breaks open which is allows cell's ribosomes to get access to the RNA and produce the desired protein.

 

"Once we had worked out how to use Toehold Switches and RNA molecules to encode the basic logic operations - AND, OR, and NOT, we were able to condense this functionality within a carefully designed molecule that we call a gate RNA. Use of a gate RNA makes the Ribocomputing Devices much more genetically compact and helps with scaling up the circuits so that the cells can make more complex decisions," said co-first and co-corresponding author Alexander Green, Ph.D.

 

The usage of these Ribocomputing Devices is not restricted to living organisms, they can be used in cell-free applications. As these logic-based RNAs could be freeze-dried on paper and thus boost the possibilities of paper-based biological circuits. These paper-based biological circuits can enhance approaches.

 

The mysteries behind human living cells are being explored and even utilized; the development of these living circuits is just the first step in a long road to cure all diseases. The reported breakthrough shall facilitate and cut the period of drug development cycles and thus it is expected in the near future the accreditation a lot of drugs for different diseases.

 

doi:10.1038/nature23271

Source: https://wyss.harvard.edu/programming-cells-with-computer-like-logic/

Keywords: Synthetic biology, Logic units, ribocomputing devices, RNA.

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