Part 2: Bio Patrika interviews Mr. Ghosh on his thoughts about “non‐equilibrium polymerization of Amyloid peptides”

Mr. Chandranath Ghosh’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Mr. Ghosh is currently a PhD student in the lab of Dr. Dibyendu Das (Swarnajayanti Fellow 2020) at the Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata. He published a paper titled “Non‐Equilibrium Polymerization of Cross‐β Amyloid Peptides for Temporal Control of Electronic Properties” as a joint first author in Angewandte Chemie Int. journal (2020).

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

Our group’s work in Angewandte Chemie describes the development of a unique class of soft nanomaterials through non-equilibrium amyloid polymerization. We all know about neurodegenerative Alzheimer’s disease. The key factor for such disease is the production and deposition of the β-amyloid peptide (Aβ). Detailed and thorough investigation has shown the formation of an exclusive polymorphic structure for the fibrilar deposition of peptides. This has been a constant field of interest for their distinct morphological and conformational variation for last fifty years. However, we were solely interested in designing a system that will assemble first and then disassemble on its own with time. Being inspired by the assembling nature of Aβ peptides, we selected a small part of the Aβ peptide sequence that mainly drives the assembly i.e., KLVFFAE. As our primary objective was to create a system that breaks apart from its assembled state without any mechanical or external influence showing the negative feedback loop, we have modified the core sequence as HLVFFAE (replacing lysine with histidine). This small peptide sequence will act as building blocks and self-assemble when it becomes activated, coupling with para nitrophenol. Hence an out of equilibrium state is achieved through these transiently formed cross beta-amyloid networks.

Figure 1. Schematic representation of work.

“[…] first to show a closer resemblance with the microtubule formation through a minimalistic peptide sequence acting as self-assembling building blocks.”

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

Scientist needs to focus on choosing problems based upon its impact on the scientific and non-scientific community. The perennial attempt to understand the fundamental concepts of natural phenomena and mimic the mechanisms in an organized and more straightforward fashion is the most challenging task in modern science. Despite being an emerging field, Systems chemistry has already made room in the top areas of world science. Being a part of this newly emerged community, we are also fascinated with the natural phenomena like the polymerization and depolymerisation of the microtubule systems. We believe that a stepping stone has been employed to design systems with sustained autonomy through our current work. A considerable number of attempts by many groups have already been done in materializing such a beautiful concept observed in nature. However, our group is the first to show a closer resemblance with the microtubule formation through a minimalistic peptide sequence acting as self-assembling building blocks. In the current work, we have exploited the hydrophobic collapse in peptide sequences to access the non-equilibrium state transiently. Characterization from different analytical techniques e.g. spectroscopic analysis and microscopic observation, has helped us to conclude that indeed accelerated catalysis from the polymerized amyloid state is happening, which subsequently degrades the fuel from the assembled state.

The most intriguing aspect of this work is attributed to showing the temporal control over the observed transient system’s functionality. The transitorily formed amyloid network has shown maximum conductivity when the out of equilibrium state is reached. This transient enhancement happens due to the paracrystalline packing of the beta-sheets, which increase the proximity of the aromatic residues. The design strategy of such an autonomous microsystem can be used as active materials for different areas like biosensors, molecular drug delivery etc.

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

In research work, eureka moments appear only when a hypothesized concept and challenging experiments turn up with expected results. Nonetheless, the main job lies in analysing the data obtained by different experiments. Even a negative result can give us hope if we evaluate the data minutely and figure out the cause of such consequence. Although we were confident about our hypothesis, it was yet to be established through a set of experiments. We were getting indications from some initial data that were correlating with our premise. But I was really delighted when the expected result matched the experimental data that is considered the gold standard in this field. The experiment is congo red binding with the peptide assembly. Congo red is a well-known dye that has been used for peptide assembly assay for the last fifty years. We have seen that our designed short peptide binds well with CR when it assembles and forms a dense network. The binding gets loosened when the network is disrupted with time. This binding and de-binding was indicated with the corresponding red and blue shift from the congo red signature absorption maxima at 495 nm. This was indeed a fascinating outcome for us, instantly changing the vague scenario and making us super confident about our proposition.

What do you hope to do next?

As I have said earlier, the current work is a stepping stone to create a self-sustained autonomous system that can transiently achieve the out of equilibrium state. Our venture will be continued in exploiting the peptide-based nanostructures for their function and structural diversity. Currently, we have started working on the catalytic efficiencies of these peptide nanostructures following the suitable design strategy and structure-function relationship.

Where do you seek scientific inspiration?

I have always been wondered while thinking about the universe. Science has lifted many veils from the microcosmic wonders of atoms to the mega marvels of the universe and revealed many things beyond our limited understanding. The journey of science for the continuous effort to reach the truth has always fascinated me. My scientific journey with my mere limited ability has been driven by such insane but fundamental curiosity.

“The scientist is not a person who gives the right answers, he is one who asks the right questions.”

How do you intend to help Indian science improve?

I have the privileged opportunity to pursue my doctoral study at IISER Kolkata under the supervision of Dr. Dibyendu Das, one of the most promising scientists working at present in our country. As a group of systems chemists our continuous effort is engaged in making artificial systems that are inspired by natural occurrences. Here, I would like to mention the quotation by Claude Levi-Srauss. “The scientist is not a person who gives the right answers, he is one who asks the right questions.” Following this utter fundamental statement, we would like to raise the vital questions that would cater to the scientific and non-scientific community of our country and find the probable solutions using our fullest potential.

Reference

Bal S#, Ghosh C#, Ghosh T, Vijayaraghavan R K, Das D, Non‐Equilibrium Polymerization of Cross‐β Amyloid Peptides for Temporal Control of Electronic Properties. Angew. Chem. Int. Ed. 2020, 59, 13506. #Equal contribution.

Email: chandranath244@gmail.com

Learn more about Dr. Das lab research interests https://www.ddaslab.com/.

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