Cells in our bodies communicate important messages via interactions between proteins. In order for these messages to be clearly and accurately conveyed, every protein needs to talk to only one other partner, cutting out any crosstalk with other similar proteins.
A new MIT study has unveiled how crosstalk between these proteins can be avoided by using cells. Furthermore, the study has also shown how there are many more potential protein interactions that cells have yet to use.
This could assist synthetic biologists in creating new pairs of proteins to act as artificial circuits — which would be useful when diagnosing diseases.
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New study and new combinations
The MIT researchers created new pairs of signaling proteins to show how these can be useful in linking new signals to new outputs by engineering E. coli cells.
"Using our high-throughput approach, you can generate many orthogonal versions of a particular interaction, allowing you to see how many different insulated versions of that protein complex can be built," said Conor McClune, an MIT graduate student and the lead author of the study.
A team led by @conor_mcclune and @michael_laub8 has developed a method to build proteins while avoiding crosstalk with existing molecules. Such engineered signaling pathways could offer new ways to build synthetic biology circuits: https://t.co/lxk21wxC6npic.twitter.com/olTkVZeqeG— MIT Biology (@MITBiology) October 23, 2019
In their study, the researchers used a two-component signaling pathway that is found in bacteria. These pathways have evolved through a process that allows cells to duplicate genes to signal proteins they already have. Then they mutate them and end up creating similar protein groupings.
“It’s intrinsically advantageous for organisms to be able to expand this small number of signaling families quite dramatically, but it runs the risk that you’re going to have crosstalk between these systems that are all very similar," said Michael Laub, MIT professor of Biology and senior author of the study.
Laub continued, "It then becomes an interesting challenge for cells: How do you maintain the fidelity of information flow, and how do you couple specific inputs to specific outputs?"
Finally, Laub said, "What we found is that it’s pretty easy to find combinations that will work, where two proteins interact to transduce a signal, and they don’t talk to anything else inside the cell."
What the study also assists with is a new strategy for creating synthetic circuits. One of the applications could be designing circuits that notice the presence of other microbes. These circuits could prove useful when creating probiotic bacteria, which helps diagnose infectious diseases.
"Bacteria can be engineered to sense and respond to their environment, with widespread applications such as ‘smart’ gut bacteria that could diagnose and treat inflammation, diabetes, or cancer, or soil microbes that maintain proper nitrogen levels and eliminate the need for fertilizer," said Jeffrey Tabor, an associate professor of bioengineering and biosciences at Rice University.
Tabor continued, "To build such bacteria, synthetic biologists require genetically encoded 'sensors.'"
Furthermore, if adapted for use in human cells, the new study's approach could also assist biologists in designing novel ways to create human T cells, which destroy cancer cells.
The study was published on Wednesday in Nature.