An engineer’s winding but rewarding journey into biology - IndiaBioscience


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Sreenath Balakrishnan is an Assistant Professor at the Indian Institute of Technology (IIT) Goa. He is one of the Young Investigators selected to attend YIM2020 in Mahabalipuram. In this invited article, he writes about applying insights from his training as a mechanical engineer to biological problems and about the rapidly growing field of bioengineering.

Research has become increasingly interdisciplinary and an exciting multidisciplinary field is bioengineering. Research in this area over several decades has produced many applications such as medical implants, engineered tissues, and brain-machine interfaces. The current excitement around synthetic biology and artificial cells further necessitates the infusion of engineers into life sciences. However, the number of engineers trained in traditional disciplines such as mechanical, electrical and computer science venturing into bioengineering remains abysmally low, especially in India. By sharing my meandering journey, I hope to convince young engineers to become bioengineers and allay the insecurities of those in the making.

My first impressions of biology were repulsive. As a child, the suitcase full of thick books that my brother, who was ten years elder to me and pursuing medical school, brought home during his vacations sounded an early alarm. Having to remember many facts and names further alienated the subject and I chose computer programming over biology during my higher secondary.

Later, while pursuing a BTech in Mechanical Engineering, I had my first tryst with biology during an unsuccessful attempt at creating a bi-pedal walking mechanism. Naively, a friend and I hooked up four motors to a frame for replicating the two hip and ankle joints. When the robot couldn’t balance, we realized a subtle aspect of walking. Before lifting a leg, our hips move laterally to shift the centre of gravity above the other leg, which is on the ground. After BTech, I worked for two years with Larsen and Toubro, wherein I got a once-in-a-lifetime opportunity to be part of the team that built INS Arihant, India’s first indigenously-built nuclear submarine.

Subsequently, I moved to Virginia Tech for their master’s program in Mechanical Engineering. I secured a research assistantship position with Rolf Mueller who was working on echolocation in bats. We studied a fascinating behaviour in horseshoe bats – they actively deformed their outer ears while echolocating. My contribution to this project was a digital model that mimics these motions. During the project, I developed an interest in biology, which was further piqued by a graduate course on bio-inspired technology taught by Mueller. I also realized the passion with which people work in academia and started considering becoming a faculty. Here was a job that pays you to do what you like to do!

After completing my master’s degree, I took a detour from research and decided to pursue a life-long dream of working on a socially-relevant project in India. After several interviews, I chose the MindTree Foundation and joined a project for enabling computer access for people with motor disabilities such as cerebral palsy. By the time I joined, the team had decided to develop a device for recognizing hand gestures and had built a glove fitted with accelerometers. I was entrusted with creating an algorithm for recognizing gestures from the accelerometer signals.

After poring over various machine learning techniques over several months, I reverted to mechanics and modelled fingers as linkages. I used inverse kinematics, a technique to analyze linkages, which I had learned during my bachelor’s degree. Looking back, I can relate one of my favourite quotes by G.K. Ananthasuresh, my then-future PhD advisor, ​“Your undergraduate education always stays with you.” By the time I successfully demonstrated the algorithm, the Foundation was on the verge of closing due to troubles in its parent company, Mindtree Ltd., and had to discontinue this project.

Stung by this setback, I returned to academic research and joined G.K. Ananthasuresh’s lab at the Indian Institute of Science (IISc), Bengaluru, as a research assistant. Time spent on the beautiful IISc campus cemented my aspirations to become a faculty. I had decided to apply for a PhD position in IISc when a poster on my lab notice board caught my attention; it was for a new PhD program in Bioengineering.

All my past experiences, bi-pedal walking robot, modelling bat ears and hand gestures seemed to align with this program, and I instinctively applied for it. My interviews went well, and I was selected among the first batch of bioengineers at IISc. Our batch had a healthy mix of biologists and engineers, and the program was carefully designed to complement our previous training through theory and lab courses.

I had chosen to work on the mechanical properties of liver cells with Saumitra Das in microbiology and G.K. Ananthasuresh in mechanical engineering. In my first interaction with Saumitra Das, he gauged my apprehension and told me that ​“Biology taught in class can be boring, but practical biology is exciting.” This vindicated my initial discomfort with biology which had subsequently changed to enthusiasm. I decided to embrace the subject rather than shy away from it.

Even though I had started to understand the subject from my batchmates and lab meetings, I still found the descriptive nature, without quantitative principles, of standard biology textbooks such as Campbell’s and Lehninger’s unsuitable to my taste. Luckily, I found ​‘Physical Biology of the Cell’ by Rob Phillips, which introduced biology from a physical and quantitative viewpoint using principles such as energy, entropy and diffusion. The book followed a novel approach of introducing biological systems and processes based on their physical proximity such as length and time scales, and energies involved. This fascinated me and even helped me clear my comprehensive examination!

My research started in the usual way engineers are expected to contribute in biology, by building experimental tools and methods. I developed a perfusion culture system, for culturing cells under flow, and coded image processing algorithms for obtaining the geometry of the nucleus from microscopy images. By using these techniques, I made a primary observation that liver cells with Hepatitis C Virus have larger nuclei than normal liver cells.

While I was progressing with biochemical and biomechanical experiments for understanding the molecular mechanisms responsible for this phenomenon, a question by G.K. Ananthasuresh intrigued me. He asked whether I could discern the molecular mechanism from just the changes in nuclear shape. This innocuous query took me on a ride to understand the cell and nucleus as a mechanical structure and further model the nuclear envelope using mechanics of membranes. I was elated when the predictions from my model matched with experiments.

Soon after defending my PhD thesis, I applied for faculty positions and got recruited at the School of Mechanical Sciences at Indian Institute of Technology (IIT) Goa.

From my experience, the biggest hurdles bioengineers face are insecurities, such as wiil I ever be able to master biology, do I know enough about the subject, and am I foregoing all my previous expertise. Here are some suggestions from my limited experience and wisdom to overcome them:

  • Learn the subject from a book that takes a physical approach to biology such as the ​‘Physical biology of the cell’ by Rob Phillips and ​‘Biological Physics’ by Philip Nelson.
  • Discuss science with your peers, particularly people with a biology background. Lab meetings are especially helpful because you can understand the way biologists think and how they design and refine their experiments.
  • Make many presentations, especially to critical senior faculty in life sciences. Their questions will help you design your controls better, which will be invaluable when you are publishing.
  • Develop a unique viewpoint to your biological system aligned with your basic training. While I would relate to cells as mechanical structures, electrical engineers can view the nervous system as a network or circuit, chemical engineers can imagine cells as chemical reactors and for computer engineers, the cell could be an information processor. From this unique viewpoint, apply physical principles and techniques developed in your discipline to the biological system, which can be used, among many other things, to enhance experimental observations and discover mechanisms. In my opinion, the insight obtained from applying physical principles to their unique viewpoint would be the greatest contribution by bioengineers.

This is a companion discussion topic for the original entry at https://indiabioscience.org/columns/journey-of-a-yi/an-engineers-winding-but-rewarding-journey-into-biology

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Sir,
I’m a btech in biotechnology but I don’t find much opportunities here in India… The scenario is quite sad.
I’ve some of my classmates who regret taking biology as their core subject.