Soumya Shraddhya Paul, Amity University Noida
The Synthetic Biological Circuit plays a huge role when it comes to understanding the concept of various things especially biological processes that happens inside organisms. Through regulatory gene expression, one can get an idea about how long does it take for normal organisms to respond to the external stimulus it usually takes minutes to hours depending on the functions. Hence, scientists decided to show the different aspects of synthetic biology circuits by working on yeast cells. This Synthetic Biological Circuit was designed based on protein phosphorylation reactions that were able to respond to inputs within seconds. Multicomponent logic gates managed to provide ultrasensitivity after finding this the researchers further went down to find more about the yeast protein interactions networks with similar regulatory functions and went on to find previously unrecognized circuits which work as the native toggle switch.
Brief About the Study
In this study, the scientists created a bistable toggle switch in Saccharomyces cerevisiae using cross repression topology which contained 11 protein-protein phosphorylation elements. The toggle that was created was seen to be ultrasensitive and could generate an output or respond to input within seconds, it was also seen to show bistability. By taking inspiration from the toggle architecture and size the scientists got an idea to create computational frameworks that will help to search for more bistable networks and endogenous pathways. Through this study, scientists were able to find five unrecognized endogenous pathways that showed bistability and they were able to prove their existence experimentally. The general idea of this study came from the fact that natural biological processes like signal transduction and metabolism use reversible protein-protein interaction networks and works and a higher speed.
In this study, the basic idea was to create a “prosthetic network” that will show various behaviors and help us understand various endogenous networks.
Results
In this study, the scientist created a bistable toggle switch in Saccharomyces cerevisiae using reversible protein-protein-based interactions (as mention above). The network uses encoded positive feedback regulation that comes from two branches which are arranged in such a way that they repress each other also known as multi cross-repression and also generate two inputs between the two possible states of the system. This engineered network is developed from 11 phospho-in and phospho-out transduction elements that have exogenous chimeric fusion proteins and endogenous proteins from the high-osmolarity mitogen-activated protein kinase (MAPK) pathway.
This showed that the toggle networks respond to the external inputs within seconds and also respond to very low input signal concentrations making it ultrasensitive. Due to the creation of bistable networks the scientists were motivated to created computational frameworks for searching endogenous networks that will show similar bistability.
A search was conducted within Saccharomyces cerevisiae for toggle networks in the endogenous pathway from two to nine nodes in length, this showed 109,401 candidates. Out of this 186 candidates could be experimentally tested and out of this it was seen discovered five previously undiscovered protein-protein interaction networks that showed bistability.
Conclusion
Through this study, it was seen that a bioengineered fast, stable toggle network made up of reversible protein-phosphorylation interactions and framework can help find bistable toggle networks in natural settings. In the future, this discovery can help uncover furthermore interactions, as well as protein-protein interaction networks, which can enable bioengineers to create fast sensing and processing which can function in real-time.
Also read: Innovative shape–actuated electronic for Spinal Cord Stimulation
References:
- Mishra, D., Bepler, T., Teague, B., Berger, B., Broach, J., & Weiss, R. (2021a). An engineered protein-phosphorylation toggle network with implications for endogenous network discovery. Science, 373(6550). https://doi.org/10.1126/science.aav0780
- Synthetic biology circuits can respond within seconds: https://phys.org/news/2021-07-synthetic-biology-circuits-seconds.html
About author:
Soumya Shraddhya Paul is an undergrad biotechnology student who worked in building 3D prosthetics in Base Hospital Delhi Cantt, and holds a key interest in nutraceuticals and enzymology.
Social Media Info: www.linkedin.com/in/soumya-shraddhya-paul-858229203
Some of her published articles at BioXone are:
2 thoughts on “Synthetic Biological Circuit for faster response”