Part 2: Bio Patrika interviews Mr. Mahato on his thoughts about “Chemical evolution, logic gates and amyloid nanotubes”

Mr. Chiranjit Mahato’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Mr. Chatterjee is currently a project JRF in the lab of Dr. Dibyendu Das (Swarnajayanti Fellow 2020) in the Department of Chemical Sciences of Indian Institute of Science Education and Research (IISER) Kolkata. He published a paper titled “Complex Cascade Reaction Networks via Cross β Amyloid Nanotubes” as the joint first author in Angewandte Chemie Int journal (2020).

How would you explain your paper’s key results to the non-scientific community?

Our recent work recently got published in Angewandte Chemie gives a brief idea of complex cascade reaction networks via cross β amyloid nanotubes. This type of reaction in biological systems was shaped through millions of years ago and plays a critical role in cellular metabolism, signal transduction, and so forth. Alzheimer’s disease is caused due to the abnormal fold of a protein in and around the brain. That protein is known as amyloid. Many research groups showed that amyloid could be used as a functional material.

Firstly, we have designed a peptide sequence (Im-KLVFFAL-NH2) which contains the hydrophobic nucleating core (17LVFFA21) of beta-amyloid (Aβ), which assembled to form nanotubes. We wanted to utilize the binding capabilities of imidazole exposed paracrystalline surface of that amyloid nanotube, so we have added hemin (a prosthetic group) and sarcosine oxidase (a small enzyme, SOX) to the medium and form a nanohybrid (Im-KL-hemin-SOX). Due to the interaction between imidazole and hemin, our amyloid nanotube showed the peroxidase activity. For our purpose, using this nanohybrid (Im-KL-hemin-SOX) we have performed two-step, three-step, and more importantly convergent cascade (Fig. 1).

Figure 1. Schematic representation of different types of cascade reactions in the presence of Im-KL-hemin-SOX conjugate.

Finally, a three-input Boolean logic gate was formed by SOX, hemin and Im-KL as chemical inputs and chromogenic product ‘tetraguiacol’ as output. Interestingly, when all chemical inputs were present there at that time only we got the output (Fig. 2a). Absence of any input did not give us the output. So we understood the importance of all the components in the hybrid system. A more complex logic network has been designed for the representation of convergent cascade where SAR-GU and water are the input of the first AND gate and chromogenic tetraguiacol is the output (Fig. 2b).

Figure 2. a) Three input logic gate (by nanotube, SOX and hemin as chemical input) b) Logic networks for the representation of convergent cascade.

What are the possible consequences of these findings for your research area?

Our work is the first example where only one small enzyme has been used instead of a higher no of large-enzyme to design a convergent cascade, which may contribute to the possibility of the use of our hybrid system (nanotube-enzyme-hemin) in a harsh condition also. Mimicking such type of complexed reactions networks will give new direction for finding in multianalyte biosensor and can find relevance for accurate diagnostic applications. We have designed a logic gate in wet conditions utilizing multiple biologically important stimuli as inputs while providing useful outputs (color, fluorescence, etc.) can be useful in processing the chemical/biochemical information.

“[…] designed a logic gate in wet conditions utilizing multiple biologically important stimuli as inputs while providing useful outputs (color, fluorescence, etc.) can be useful in processing the chemical/biochemical information.”

What was the exciting moment (eureka moment) during your research?

Designing a multistep chemical reaction is a kind of game. In my life, I was always fascinating to select chemistry as a carrier, especially in the research field. So, after joining IISER Kolkata in Dr. Das’s group as a project student, I was working in out of equilibrium self-assembly. One day when Ayan da presented the idea of designing multistep reactions, I think that’s the moment when I truly attracted to amyloid nanotube because of their binding ability, compartmentalization ability and mimicking ability. For the designing of multistep reaction networks, the colocalization of hemin and sarcosine oxidase was an important point of the whole study, when we have seen the colocalization of hemin and SOX in CLSM made us more confident to reach the logical conclusion. After the addition of SAR-GU to the reaction mixture, when the color of the reaction medium was changing due to the generation of tetraguiacol, that was the eureka moment during our whole study.

What do you hope to do next?

Our next target is to design a peptide-based motor that can mimic nuclease enzymes. Breaking of the inert phosphodiester bond in DNA double helix is key attention for many years due to its importance in medical treatment for therapeutic study. The design of artificial phosphodiesterase with efficient and selective cleavage ability will give a new direction in the diagnosis of protein-related disease.

Where do you seek scientific inspiration?

Nature is full of surprises; humans are still trying to understand how life got started. Scientists are always trying to find the root of evolution. And I think chemistry is a key factor to go deeper into it. So I got primary inspiration from nature. In terms of research work, a good H-NMR of our prepared substrate for catalysis makes me so happy and fueled me to reach up to lead data for our project. Finally, when we get a lead result after months, makes me feel that our concept is right and our way will reach the expected point.

How do you intend to help Indian science improve?

India has a long civilizational history of scientific achievement. But today if you see the list of Indian scientists who have won Nobel prize, it begins and ends with C.V. Raman. Last year India was the third country in the number of publishing research articles. So it’s not like that science is not improving in India. The current pandemic has shaken us and simultaneously made us realize the importance of scientific research. The quality of better infrastructure and more investment in research and development of basic scientific research as well as in the interdisciplinary field can lead to better achievement in Indian science.

The wide range of applications of biosensors which includes medicine, environment and agriculture makes it a valuable asset in the field of interdisciplinary research. Amyloid may play a vital role in this field. Though the development of different types of functionalized amyloid materials got high attention for the last few decades. Because these type of amyloid based nanostructures provide excellent biocompatibility, rich phase behaviors, and showing versatile interaction with the surface. There is a lot of space in the development of amyloid based artificial enzyme and the protein-related disease diagnosis procedure. Overall, functional amyloids have excellent potential applications in next-generation biotechnology and biomaterials. Very few scientists from India are working in this field, so for me, it is a perfect opportunity to work in this field and put my contribution to improve Indian science.

Reference

Chatterjee A#, Mahato C# and Das D. Complex Cascade Reaction Networks via Cross β Amyloid Nanotubes. Angew. Chem. Int. Ed. (2020), doi:10.1002/anie.202011454. #Equal contribution.

Email: cmahato50@gmail.com

Lab webpage: https://www.ddaslab.com/

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