Work done in the lab of Prof Nikolay Dokholyan at Penn State College of Medicine, PSU, Hershey
Dr. Yashavantha Vishweshwaraiah has completed his Ph.D. under the supervision of Prof. Balaji Prakash at Central Food Technological Research Institute, Mysore. During his doctoral studies, he worked on understanding the structure-function relationship in plant lectins and on engineering antibacterial peptide inhibitors. In February 2019, he joined the Dokholyan lab at Penn State College of Medicine, PSU, where he works on engineering novel proteins.
In simple terms, we have used a protein to create a transistor-like logic gate, which is a kind of computational operation in which several inputs control the output (Fig. 1). This is a first step in building complex nanoscale computers. These logic gates or computing agents in general, will allow us to gain a deeper understanding of human biology and disease and open up opportunities for the development of precision therapeutics.
Our group is working on the development of approaches to sense and control proteins in living cells. We have been developing nano computing agents for the targeted regulation of cellular activity. These computing agents respond to any given input and return the desired output signal. The conceptual architecture of a nano computing agent consists of a primary unit, which is the main protein chain. Functional modulators that respond to various signals such as light, drug, pH, temperature, or other user-defined inputs control this primary unit. For example, our logical gate in this study comprised of two sensor modules designed to respond to two inputs— light and the drug rapamycin. The wiring of these functional modulators is done through allosteric networks so that they do not interfere with any of the other functions of the protein, which means these sensor modules are stealthy. ‘Bio-programming’ using these computing agents would enable direct interrogation of biological systems.
It’s a proof-of-concept work. The architecture presented in this work can be extended to many other proteins. I believe this approach will pave the way for building more robust and complex nano computers with potential applications in biomedical and biotechnological fields.
What we designed is just a first step. We are hoping to build more complex and robust nano computing agents for biological computations.
The best and most exciting part was activating the protein. The activation part was the first module we created. As soon as we activated the ‘on’ switch, we could see the changes in the cell within few minutes.
What we designed is just a first step. We are hoping to build more complex and robust nano computing agents for biological computations.
My scientific inspiration comes mainly from reading literature. My research mentors also played a major role. Dr. Dokholyan, Dr. Balaji Prakash and Dr. Lalitha Gowda will be my constant source of inspiration.
I firmly believe that public engagement with science is the need of the hour. The public lack access to scientific information. Scientific posts and YouTube contents in local languages (in lay terms) could be some of the strategies. One of my interests is to communicate science in the rural region of India, especially with the school children and the younger generation.
Vishweshwaraiah, Y.L., Chen, J., Chirasani, V.R. et al. Two-input protein logic gate for computation in living cells. Nat Commun 12, 6615 (2021). https://www.nature.com/articles/s41467-021-26937-x
Edited by: Dolly Singh