Conversation with Shantanu Sen
In conversation with....
Shantanu Sen
PhD student of Prof. Sandeep Verma, on his recent study: “Synthesis of a highly thermostable insulin by phenylalanine conjugation at B29 Lysine”. Communications Chemistry. 2024 Jul 23;7(1):161.
MFCEM: Hi Shantanu! At the onset let me congratulate you and your mentor Prof. Sandeep Verma, on this immensely relevant study, and for the many recognitions for this spectacular innovation.
The figures are alarming- according to the IDF, currently, 537 million adults are living with diabetes, and every 3 in 4 adults with diabetes live in low- and middle-income countries. Worse is the fact that these numbers are predicted to rise further. With this in mind, could you please highlight for our readers the relevance of your study, after which we would talk about the science that went into it.
Shantanu Sen: Thank you for recognizing our contribution and providing us with this wonderful platform to talk about it. The relevance of our study lies in addressing a critical gap in the storage and transportation of commercial insulin, a life-saving medication for diabetic patients. Current insulin formulations require continuous refrigeration, which is challenging in low- and middle-income countries with unreliable power supply and limited cold-chain infrastructure. This dependency not only affects underprivileged communities but also poses challenges for privileged users. Our work on thermostable insulin, enhanced by protein conjugation technique, aims to eliminate these constraints, ensuring insulin remains effective for longer duration even under non-refrigerated conditions and thus providing independence for their carefree usage. This innovation has the potential to revolutionize insulin storage and distribution globally, making it more accessible and reducing wastage.
MFCEM: The thermostable phenylalanine-conjugated insulin, termed FHI in your study was one of the many modifications that you tried; could take us through the thought process behind the choice of the modifications; what were the experimental challenges you faced? How did you overcome them?
Shantanu Sen: The choice of modifications was driven by the need to improve insulin's thermostability while preserving its biological efficacy. The chemical synthesis of this novel human insulin derivative involved conjugating a phenylalanine amino acid to the side chain amine of the B29th lysine residue of human insulin. This strategic incorporation of an additional aromatic amino acid at a specific position enhances the thermostability of the modified insulin by maintaining its structural integrity over extended periods, even under extreme unfavourable conditions.
Experimentally, synthesizing the modified insulin required precise chemical conjugation and concerns about compromising its biological efficacy. To address these, we optimized extensive reaction conditions and employed advanced techniques to predict and confirm the enhanced stability and preserved bioactivity of the modified insulin. These efforts were made possible through close collaboration among synthetic chemists, biologists, and computational experts, ensuring that the modified insulin remained effective under rigorous testing conditions.
MFCEM: Since the initial breakthrough by Authur Riggs that led to the creation of the first artificially synthesized insulin in the late 1970s, dedicated efforts continue to improve the overall efficacy of synthetic insulin as a therapeutic, such as, its sensitivity, selectivity, duration of action among others. What was the motivation to work on the stability of the protein? Where you mindful of not compromising the other properties of the insulin peptide? How did you strike a balance?
Shantanu Sen: The motivation arose from the critical need to address insulin's thermal instability, which is a major obstacle to its global accessibility. While improving insulin stability, we ensured that the modification did not interfere with its biological activities, such as glucose-lowering efficacy. To achieve this balance, we conducted extensive studies in cellular and animal models simulating diabetic conditions, confirming that the modified insulin retained its biological activity. Additionally, other experiments helped to ensure that the structural modifications did not disrupt the insulin’s interaction with cellular receptors, preserving its therapeutic potential.
I believe the key to our innovation lies in the minimal modification approach—we found the ideal spot with the right amount of chemical modification.
MFCEM: Shantanu, the immense relevance of your study is further cemented by the many recognitions that the invention attracted. You were among the top 3 winners of the Falling Walls Lab Event India, for "Breaking the Wall of Insulin Dosage Wastage"; besides, you were selected for the Gandhian Young Technological Innovation Award for the year 2023, for patented technology concerning detecting spurious aggregated insulin hormone in commercial injectable formulations. How important are these validations? Is the team, planning to take this invention to the market? could you elaborate.
Shantanu Sen: These recognitions stand as a testament to our research, emphasizing its practical impact and reinforcing confidence in its potential to tackle real-world challenges. Under the mentorship and guidance of Prof. Sandeep Verma, we are actively working to translate this innovation into a practical solution through our start-up, STABLIN BIOSCIENCES PRIVATE LIMITED. Our ultimate goal is to make these innovations widely accessible, especially in regions where cold-chain logistics are impractical, ensuring that no diabetic patient is deprived of life-saving medication.
One of the critical issues we also aim to address is the uncertainty surrounding insulin dosage quality—early-degraded insulin solution can appear as clear as fresh insulin, making it difficult for patients to visually identify without advanced testing. To tackle this, we are developing next-generation insulin variants and user-friendly methods for instant insulin quality detection before injecting.
Additionally, we are exploring applications of this research for other heat-sensitive therapeutics, such as vaccines, to overcome similar storage and distribution challenges.
Shantanu, thank you much for speaking to us, and wish you success for all future endeavours.
Conversation with Prof. R. Sankararamakrishnan
In conversation with....
Prof. R. Sankararamakrishnan
recipient of the “Distinguished Teacher Award”
IIT Kanpur, 2023
MFCEM: Congratulations Prof. Sankar for the “Distinguished Teacher Award”. What does this award mean to you?
R. Sankar: This is a huge honor and recognition for me. I thank IIT-Kanpur for this prestigious award which I will cherish throughout my life.
MFCEM: You are a structural biologist, what is your approach to teaching biology to students from such diverse disciplines of sciences and engineering at IIT-K? How do you make it relevant and engaging for the students?
R. Sankar: Biomolecular structures look complicated to begin with. However, I use visualization softwares and molecular models in the class to demonstrate the intricacies of protein and DNA structures. As the knowledge of structures helps us to understand the mechanism of the function of biomolecules, at the end of the course, the students appreciate the importance of knowing the three-dimensional structures of biomolecules. The students even after graduating from BSBE, personally contact me to convey how much they appreciate the Structural Biology knowledge gained through the course and how it helps them in their current job, be it industry or post-doc position. I have had students from engineering and experimental biology background. I really enjoyed teaching them. I start with the basics of biochemistry before getting into structural aspects of biology. I also personally talk to the students to make sure that they understand the basic concepts of structural biology. In fact after few classes, they start enjoying the structures and in many cases, they are intrigued by the beauty of nature’s work and will be curious to know why this beautiful structure is adopted and how it is important for the function of a specific biomolecule.
MFCEM: Christa McAuliffe a teacher and the first American civilian selected to go into space, famously said “I touch the future. I teach.” In today’s setting too, answers to many of the medical challenges facing our society today seem to lie at the intersection of Biology and Engineering. Having said so, how do you pique the interest of some of the brightest young minds that come to this institute, to even consider some of these challenges?
R. Sankar: Biology today is heavily interdisciplinary in nature. IIT-Kanpur is known for imparting finest training in engineering education. When BSBE Department was established, IIT-Kanpur’s vision is to utilize and exploit this ecosystem to establish frontier areas at the intersection of biology and engineering. In general, when students from engineering background want to work on biology-related problems, they generally show lot of interest in drug development, docking, bioinformatics, modeling, machine learning and simulations. My first UG student from Chemistry department worked on a structural bioinformatics project. My first M.Tech student came from Computer Science background and worked on predicting translation initiation sites using artificial neural network. I had Ph.D. students who joined in my lab with B.Tech in Chemical Engineering. My Ph.D. students from conventional biology background learned script languages like Perl and Python as part of their research projects. They have all done phenomenal work, published excellent papers and I am proud of each one of them. In all cases, when they want to do biology research, they lacked either basic biology knowledge or computational background. They are not initially confident whether they will be able to make significant contributions. However the environment in BSBE and IIT-Kanpur help them to learn the fundamentals quickly and with little encouragement, they are soon comfortable to pursue their projects. The interdisciplinary nature of biology in general and my research area in particular is a strong factor to attract the students from diverse background to take up these challenging projects.
MFCEM: Were there any teachers who left an indelible mark on you? Would you like to share some memories?
R. Sankar: I have a long list of teachers who inspired me and left an indelible mark on me and I thank everyone of them. My parents are my first teachers. My father was a middle school teacher and I attended his tuition when he taught one of my classmates. My mother made sure that we finished our homework in time and revised syllabus before the exams. I would like to express my gratitude to all my school teachers and especially to Mr. Sankaranarayanan Sir and Mr. Palanivelu Sir. I did my B.Sc. Mathematics and Chemistry under Double Majors system. Both the Chemistry and Maths Professors had great impact on me. I want to mention Prof. Rajaraman, Prof. Devarajan, Prof. Krishnamoorthy, Prof. Sitaraman and Prof. Venkatachari from Chemistry and Maths departments. During my Ph.D. course work, the course instructors were exceptional. Prof. C. Ramakrishnan, Prof. P. Balaram, Prof. M.R.N. Murthy and my thesis supervisor Prof. Saraswathi Vishveshwara made my transition to Biology easier. I particularly always wanted to emulate Prof. C. Ramakrishnan’s style of teaching in my class.
MFCEM: In premiere institutes of higher education such as the IITs, teaching goes together with carrying out cutting edge research and may prove a bit daunting to young faculty who join. Would you like to share some thoughts with your younger colleagues.
R. Sankar: It is an important point. While doing cutting-edge research is extremely important, teaching should not be viewed as a burden. In fact, teaching to bright minds in institutes like IITs will sharpen our knowledge and the basics will be stronger. I agree that for a new faculty, it may be bit difficult to balance both teaching and research in the beginning. With little bit of efforts, one should be able to excel in both domains over a period of time and we must keep in mind that these are not mutually exclusive. After attending your class, students may want to do some short-term projects in your lab. They may even join for the graduate program. Benefits of teaching while doing research in frontier areas outweigh any other disadvantages.
MFCEM: Thank you, Prof. Sankar, for sharing your thoughts and for your time. We appreciate it much.
Molecular Medicine all
In conversation with Shantanu Sen PhD student of Prof. Sandeep Verma, on his recent study: “Synthesis of a highly thermostable insulin by phenylalanine conjugation at B29 Lysine”.
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In conversation with Prof. R. Sankararamakrishnan recipient of the “Distinguished Teacher Award” IIT Kanpur, 2023
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Conversation with Dr. Nikunj Arunkumar Bhagat
In conversation with
Dr. Nikunj Arunkumar Bhagat
Assistant Professor
Department of Electrical Engineering,
Department of Biological Sciences and Biosciences,
and Mehta Family Centre for Engineering in Medicine.
MFCEM: Dr Bhagat, it is great to have you at IIT Kanpur. Your research straddles two disparate fields of Electrical engineering and Biomedical science. Having done a BTech and MTech in electrical engineering what drew you to apply your training to Biological/Medical problems?
Digital Medicine all
In conversation with Dr. Nikunj Arunkumar Bhagat
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The Bhupat & Jyoti Mehta Family Foundation
MFCEM at the Indian Institute of Technology Kanpur is generously supported by the Mehta Family Foundation.