Hitting The Bull’s Eye: Nanorods as Protein Aggregation Inhibitors

Work done in the lab of Dr. Neha Jain at Indian Institute of Technology Jodhpur

About author

Khushboo Rani is a third year PhD candidate in Dr. Neha Jain’s lab in the Department of Bioscience and Bioengineering at IIT Jodhpur. In Jain’s Lab, she is interested in understanding the cross-talk between amyloidogenic proteins in the progression of Parkinson’s disease using different tools and techniques. She completed her graduation B.Sc. (H) Biomedical Science from Delhi University. She joined Amity University (Noida) to pursue Master’s degree in Medical Physiology. She belongs to Ghaziabad district of Uttar Pradesh. Outside her scientific interest, she loves to travel and explore new things.

Bhumika Pippal is a first year Ph.D. student with Dr. Neha Jain in the Department of Bioscience and Bioengineering at IIT Jodhpur. She joined Jain’s lab at IITJ as an M.Tech. student and started working on the role of chaperone-like proteins in Parkinson’s disease and with fascination and curiosity of the work, she later joined as a Ph.D. student. She belongs to Delhi and completed her B.Tech. in Biochemical Engineering from University School of Chemical Technology, Delhi.

Interview

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

Biomolecules such as proteins play an essential role in all living organisms. Under certain unfavorable conditions, proteins lose their original shape and accumulate, forming ordered aggregates called amyloids, which are very stable and challenging to remove once formed. Various debilitating ailments such as Alzheimer’s, Parkinson’s, Huntington’s disease, and systemic lysozyme amyloidosis are caused due to amyloid deposition in different body parts. The presence of amyloids makes these diseases almost impossible to cure. One of the strategies to overcome these diseases is to stop proteins from accumulating at an early stage. Many modalities have come up. However, nanotechnology-based platforms are the most lucrative approach due to their superior stability and high loading capacities.

Our lab is intrigued by the phenomenon of amyloid formation and inhibition by different proteins involved in disease initiation and progression. The present study was exploratory and curiosity-driven, which led to a beautiful outcome. Gold is known to be an effective curative agent in many diseases. However, the efficacy depends on the structure it acquires. This is the challenge we posed to ourselves to design gold nanorods with different ratios of length and diameter. After a couple of iterations in collaboration with Mr. Shubham from Dr. Raviraj Vankayala’s lab, we successfully made gold nanorods with three distinct ratios that we characterized through various standard methods. The next challenge was to test if these nanorods would work to stop protein aggregation at an early stage. We used two commonly available proteins, hen egg white lysozyme (HEWL) and bovine serum albumin (BSA), to test our hypothesis. We used various biophysical assays to monitor protein aggregation in HEWL and BSA without and with nanorods of different ratios. Seeing our hypothesis working was a moment of true joy; the nanorods stopped protein aggregation. More importantly, as we expected, this process was dependent on the ratio of length and diameter of the nanorods.

How do these findings contribute to your research area?

With no cure or definitive treatment for amyloid-related diseases, researchers constantly look for modalities to prevent, halt and eliminate toxic species formed during protein aggregation. Moreover, identifying biocompatible systems that can cross the blood-brain barrier is the major challenge in the field. Our findings on nanorods will move the field of amyloid biology further, where these systems can be tested on animal models and have therapeutic potential against many deadly diseases due to protein aggregation.

What was the exciting moment during your research?

The most exciting part for us was to control the dimensions of nanorods and show the effects of these dimensions on protein aggregation. These are microscopic entities that need much care to be handled. Once we observed that our nanorods were working the way we thought, we rushed to visualize them under a high-end electron microscope to ensure our observations were correct and not an artifact in the system. We then performed an array of experiments to confirm our results and test the robustness of the system that we had generated. Furthermore, to our pleasure, we succeeded in all!

“Our findings on nanorods will move the field of amyloid biology further, where these systems can be tested on animal models and have therapeutic potential against many deadly diseases due to protein aggregation.”

What do you hope to do next?

Dr. Jain’s curiosity-driven lab is where we ask many questions and float many ideas around the protein aggregation mechanism. More specifically, we are interested in understanding the role of different chaperones-like proteins, chemical and artificial chaperones in reducing the burden of protein aggregation diseases using different tools and techniques. These studies not only allow us to understand the mechanism better but will also allow us to understand the intricacies that exist due to protein-protein interactions that may lead to protein aggregation.

We look forward to deciphering some of these mechanisms to move the amyloid field forward. In the process, we aim to identify novel entities with therapeutic values to contribute towards reducing the global burden of neurodegenerative diseases.

Where do you seek scientific inspiration from?

We seek primary scientific inspiration from our advisor (Dr. Neha Jain) and highly motivated lab members. Their excellent working nature and sincerity towards research give us the courage and inspiration to pursue the research and ask complex inquiries. We also live inspired by the great science and immense support from our academic grandfathers (Prof. Samrat Mukhopadhyay and Prof. Matthew Chapman).

How do you intend to help Indian science improve?

We draw scientific inspiration from many resources. We believe the Indian science domain has much potential and would support and encourage scientific ideas in our domains. Science is a collaborative effort vital to the mutual exchange of knowledge, problem-solving, innovation, and lifelong learning to develop skills for a better life. Our lab is also heavily involved in outreach activities where we visit schools in rural areas of Rajasthan, straightforwardly communicate science and motivate them to pursue a scientific career.

Reference

Rani K, Pippal B, Singh SK, Karmakar A, Vankayala R and Jain N. Effects of the aspect ratio of plasmonic gold nanorods on the inhibition of lysozyme amyloid formation. 2023 RSC Biomater. Sci.

https://doi.org/10.1039/D3BM00400G

Copy Editor

Kshipra S. Kapoor

Ph.D. candidate at Rice University

Kshipra has completed Bachelor’s in Biomedical engineering from University of Mumbai where she was the recipient of institute gold medal and university bronze medal for obtaining the highest GPA in her cohort. She received her master’s degree in Electrical and Computer Engineering at Rice University. She is currently a Ph.D. candidate at Rice University, where she is working with Prof. Raghu Kalluri in the field of exosomes. Specifically she is interested in dissecting the exosome heterogeneity between healthy and cancer cells-derived nanovesicles and advancing the understanding of exosomes classes in cancer. In her spare time, Kshipra enjoys keeping fit, cooking, calligraphy and family & friends.

Kshipra is also involved in various professional development programs and as a first generation-PhD student is helping amplify the voices and stories of minorities in her field via the global organization she is part of snevresearch where she manages the events.

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