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The unconventional behaviour of protein aggregation kinetics

Work done in the lab of Prof Soumen Das at School of Medical Science and Technology, IIT Kharagpur.

About author

Prasoon Awasthi is curious to understand the physics of biology. In this quest, currently, as a Ph.D. student, he is exploring the electrical properties of protein aggregation in different conditions. He worked on the blood pH sensor during his M.Tech. program (2014-2016) in Medical Imaging and Informatics specialization at SMST, IIT Kharagpur. He completed his B.Tech. (2010-2014) in Electronics and Communication Engineering from Gurukula Kangri University, Haridwar.

Interview

How would you explain your research outcomes to the non-scientific community?

As the age increases, we sometimes see many people, whether our relatives or neighbours, who gradually start forgetting names, faces, getting trouble remembering new things, etc. It is Alzheimer’s disease, which causes all these detrimental problems. It is estimated that approximately 44 million people are living with this disease worldwide. The main reason for Alzheimer’s disease is the aggregation of amyloid-beta (Aβ) protein.

Now, what does protein aggregation mean? Proteins are biopolymers of amino acids, and they can have four levels of structures such as primary structure (linear sequence of amino acids), secondary structure (α-helix spring-like shape, β-sheet pleated structures, etc.), tertiary structure, and quaternary structure. Being functional macromolecules, they perform various jobs to keep us alive. A single protein (or monomeric protein) constantly changes its structure to stabilize it by folding and unfolding its 3D structure. But, when the misfolding of the monomers occurs, they start losing their folded structure and its associated function. Further, the monomers bind together and form fibrils; this process is called protein aggregation or amyloid polymerization process, as shown schematically in Fig. 1. Scientists are exploring the kinetics of protein aggregation that how this aggregation evolves with time.

This problem is being explored at constant temperature conditions, whereas a temperature gradient has been observed in the human body at different locations such as the brain, deep tissues, etc. So, we endeavour to address the kinetics of protein aggregation at a temperature gradient condition. We postulate a feasible theory and numerically solve the kinetic equation, and the results demonstrate the unconventional multi-sigmoidal behaviour of protein aggregation kinetics.

How do these findings contribute to your research area?

If we revisit the studies of protein-drug and protein-protein interactions at the temperature gradient condition, this will surely provide new insights, which will be helpful for drug designing. Also, in biopharmaceuticals, protein aggregation occurs due to temperature fluctuations during production, storage, and transport; this work could contribute to understanding the maximum tolerance of temperature variation for protein aggregation.

“this work could contribute to understanding the maximum tolerance of temperature variation for protein aggregation”

What was the exciting moment during your research?

After realizing the concept of temperature gradient existence in physiology and its necessity to be included while modelling the phenomena, I solved the model system at a temperature gradient condition for the first time and obtained the multi-sigmoidal behaviour of protein aggregation kinetics rather than sigmoidal. That was my delightful moment.

What do you hope to do next?

We are studying another condition responsible for protein aggregation in the microfluidic device. This will be productive for developing an amyloid-based scaffold for engineering new materials to diagnose pathogens.

Where do you seek scientific inspiration from?

I get fascinated by many interesting phenomena occurring in nature around us, seeing different instruments, seeking knowledge of people from various backgrounds working on finding solutions to many problems. I remember that during my school days, once my uncle Shri Jagdish Chandra Awasthi brought me a test tube, a funnel, and 96-well plates; after seeing those items, I was pretty excited to carry out my science experiments.

How do you intend to help Indian science improve?

I want to contribute to Indian science by exploring collective cell migration, especially during morphogenesis, and how protein aggregation impacts cell migration behaviour. I have plans to make a dedicated group of researchers to address the unsolved problem of biophysics and start an Indian journal for this field. Also, I would like to contribute towards and promote citizen science in our country.

Reference

Prasoon Awasthi and Soumen Das. Kinetics of protein aggregation at a temperature gradient condition. Soft Matter, 2021,17, 9008-9013. https://doi.org/10.1039/D1SM00857A

Edited by: Manveen K Sethi

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