My First (and hopefully not last!) Interview

This interview featured in the In Vivo magazine, an in house magazine published annually by the Department of Bioengineering in SASTRA Deemed University. I was in my final year of integrated Masters in Medical Nanotechnology, when my juniors approached me for this interview. I hope I did some justice to the honour bestowed upon me. Do let me know in the comments! 

The link to the magazine can be found here. 

 1. You are right now working on systems biology. What would you say, are your areas of interest along with it?

My areas of interest lie in an interwoven web spun by evolution, development of organisms and the study of holistic interactions that occur amongst them. There is a fascinating background behind my motivation to work in these areas. It started with this book written by Dan Brown named Origin which raised some interesting questions related to humans’ origin and evolution. A scientist in the plot comes up with a solution in the form of an algorithm to simulate the same. This fascinated me and led me to ponder over the possibility of computation opening doors to answer several pressing questions that we couldn’t solve conventionally.

2. The number of students who work in systems biology in our college is very low and is only being realized lately. This being the case, how did you pick up on this field?

The entire credit for it goes to Dr. Chandra Mohan a.k.a., BCMR Sir, who handled my Molecular Biology course. Right after Origin, when I started learning about evolution, many of the concepts such as the organization of cells into tissues, were either difficult to understand or were against my intuition. That’s when I started interacting with BCMR sir. Discussions with him helped me realize my passion for the basic sciences and offered me clarity on not just science. We also had discussions on societal and political ideologies! And it’s him whom I have to thank for my interest in Systems Biology as well. Recognizing my knack for programming, he encouraged me to work on a modelling project for my research credits during my sixth semester.

3. We’ve often heard about Urey-Miller’s experiment which was designed to understand evolution experimentally. How do you perform such experiments computationally?

Every biological system is a complex network of chemical reactions interconnected with each other. So, we ‘instruct’ the system on what the reactants, modifiers and products are; and interconnect them by chemical kinetics. We derive the kinetic parameters from the experimentalists and their data. We plug in these parameters in our models and simulate the conditions to predict the outcomes of the model for different conditions that are difficult to experiment with. In addition, we could observe the trend of the components of the model - identify the pattern of expression, the ‘influence’ of a component on the model and so on. These components are often present in the molecular scale and hence, it’s quite difficult and pricey to observe them experimentally due to technological limitations and lack of experimental accuracy. This is where computation pitches in. It predicts the behaviour of that particular component of interest.

Science is so vast that you need more than a lifetime to learn everything!

4. You have worked under a lot of professors during your time at SASTRA, particularly with the likes of Dr. Chandra Mohan and Dr, Ashok Palaniappan. A few words on your research experiences at SASTRA.

The beginning of my undergrad research work had been a topsy-turvy one since I was observing PhD students from different labs perform their experiments whilst figuring out where my true interests lie. After a lot of thorough observations, I finally met BCMR sir and expressed my interest to work in his lab where I worked on Genome Size Evolution and Systems Biology.

My experience in BCMR sir’s lab has been quite holistic. He and his PhD scholar ensured that I learnt the basic laboratory experiments in Microbiology. I learnt how to critically analyze scientific reports. ‘Learn, Unlearn and Relearn’ is BCMR sir’s philosophy and I began to follow it too, which honed my critical reading skills. He also played a significant role in proofreading and critiquing my Statement of Purposes (SoPs) for my IAS and Khorana fellowships. So, I am really grateful to him for shaping my academic career.

Ashok sir handled Systems Biology course during my seventh semester. Following my performance in the course and previous projects, he thought that I would be a good fit into the modelling department of SASTRA’s iGEM team, and therefore encouraged me to be a part of the team. He is my guide for my dissertation works in the ninth and tenth semesters.

To sum up, I think that my time in BCMR sir’s and Ashok sir’s lab has been a good mix of learning theoretical basics and development of practical skills to put them to good use towards real-life problems.

5. As you’ve mentioned, you have also been a part of the iGEM team which won a silver medal at the Giant Jamboree last year. How was the experience of competing against teams from all over the world with your skill?

I joined the iGEM team around mid-August. Since I was also a part of the Sakura Student Exchange Programme at that time, I couldn’t be a part of iGEM during the initial phases. Our project involved the use of a toehold switch to detect miRNA biomarkers for cervical cancer. When these biomarkers bind to the toehold switch, it initiates the expression of a certain fluorescent protein. My work in this project was to model all the chemical reactions which take place right from the binding of the miRNA to the expression of the fluorescent protein. In addition to that, I helped document the procedures during the final days of the project. Although my interaction with the team was mostly limited to my team leader (and also my senior) - Priyannth R.S and my partner in the modelling team- Raghavv Raghavender Suresh, it was a really exciting and insightful experience as I learnt a lot from both of them and looked up to their problem-solving ability and way of thinking. Looking back at it, the team made a lot of effort towards the project and I am really glad it bore fruit in the form of a Silver medal and the Best Software Tool award.

6. Your academic journey has been quite the fairytale with the IAS and Khorana fellowships and the Sakura Exchange program being secured. What were your significant take-home messages from these wonderful initiatives?

IAS Summer Research Fellowship Programme was my first ever fellowship. I did it under the guidance of Dr. Amit Ghosh, who is an Assistant Professor working at the Energy Sciences and Engineering department at IIT Kharagpur and his PhD scholar, Pritam Kundu. The lab focused on biofuels and my work there involved a metagenomic analysis of the microbes present in the gut of termites. Lignocellulose constitutes the major portion of biomass being produced and yet, its utilization for producing biofuels is inefficient and costly. Since termites are naturally capable of digesting wood, we studied the microbes present in their gut to identify the key ‘influencers’ that enable this process. It was phenomenal in a way because it made me learn the pivotal facets of communication - both within the microbes and amongst researchers. Kharagpur was also a beautiful place to stay - their campus being the largest one in India! It was literally in the middle of a forest - the greenery never ceasing to amaze me. Their library really amazed me as well - it is the largest University library with floors of books, journals and references from every field!

Later in the same year, I was selected along with three other students for the Sakura Exchange program to visit Tokyo City University in Japan. We were accompanied by Anuradha ma’am from the department of Bioengineering. The lab under whose invitation we went, works on Plasma Medicine, where we observed students experimenting with plasma for wound healing. In addition to that, we also got to witness biomedical engineers trying to design wireless chargers working on the principle of inductive charge transfer by stitching coils on clothes. Some others were studying the effect of sound frequencies spectrum on sleep. Most of the people we met in those labs were Masters’ students, who designed experiments themselves. It indicated to me that I have a long way ahead in my journey to reach their level of skills. Sakura was very special for me as it was my first time outside of India. Most of us know that the Japanese are amongst the kindest and hardworking people. But I feel the urge to emphasize this to everyone, having experienced it there firsthand.

My next stop was at a winter school program at the International Center for Theoretical Sciences (ICTS) in Bengaluru for a conference centered on developmental biology. There were speakers from across the world and from India - working on understanding morphogenesis from a theoretical and biological point of view. Through interactions there, I came to know about Dr Anatoly B. Kolomeisky, a biophysicist at Rice University, Texas. This 3-week school was an eye-opener for me as it made me marvel at how an interdisciplinary approach drove solutions and raised new questions in morphogenesis. When I got shortlisted for my Khorana fellowship, I contacted Dr. Kolomeisky to gain some hands-on experience in theoretical biology and luckily, he accepted, offering me a chance to work on how differentiation is initiated in development. Unfortunately, due to the ongoing COVID-19 pandemic, I am yet to work on it and I am looking forward to it!

A major lesson for me after every application was an understanding of how to write a Statement of Purpose. I think what a selection committee looks for is the passion we have towards addressing a problem statement and our thinking on how we aim to solve it. For instance, for my Khorana fellowship, I had to write a 1000- word SoP on my problem statement, motivation, experimental design and possible results and applications. I wrote my SoP based on a condition I have known as Myoclonic Epilepsy which causes seizures when I am stressed or sleep-deprived. I wanted to know the molecular circuitry behind this, to understand what happens under stress or sleep deprivation so that I could try and devise a solution for the same. This meant something to me and therefore, stood out in my SoP very well. As there weren’t any professors who worked extensively on Myoclonic epilepsy, when I did get shortlisted for the fellowship, I approached Dr. Kolomeisky to work on another area of interest.

7. We have seen you as quite the connoisseur of documentaries that deal with a wide range of themes from politics to science. What was the effect they had on you?

Credit for this goes entirely to Priyannth. His thirst for knowledge is analogous to that of a sponge soaking in water. We started watching documentaries about history, world wars, politics, corruption and science. We would then discuss the documentaries in detail - the causative agents and the what-ifs, which in turn developed our understanding of the topic. Priyannth has this habit of taking a scientific approach towards every topic of discussion, backing everything with logic. My interactions with him and our exercises molded our thinking, enabling us to ‘science’ in every-day life.

I would recommend this documentary titled Babies on Netflix. It offers an insight into the development and behavior of babies as they grow. Being someone interested in developmental biology, I had always considered the development of embryos inside the womb to be a miraculous event. But on watching this series, I realized how much of a complex environment babies are placed in on birth, and yet they learn and become integral parts of the family and society. I think there’s a lot to explore in this field for researchers and I hope the readers’ interest is piqued as well.

8. One of the most intriguing questions in developmental and evolutionary biology is the accuracy with which sexual reproduction and fetal development occur. What does it take in your opinion, to achieve this level of accuracy? Is it possible to solve these questions computationally?

This is one of the most intriguing questions in evolutionary biology! There are many such open questions in evolution, for instance, the emergence of the first protocells and even the first humans. In the book The Origin of Species, Charles Darwin laid down an elaborate method by which the human eye, which is one of the most complex organs has evolved. At every stage, small modifications that would have conferred an advantage to us were naturally selected. The contemporary human eye has a complex structure and functionality. But just like how this structure was attained over the years by modifications and selection, the same can be said for literally every other system in our body including sexual reproduction and fetal development.

To explain the second part of your question, I think I could take my dissertation work as an example. I am trying to understand the role of circadian rhythm in regulating glucose metabolism. If you come to think about it, the day/night rhythm is the one constant yet rhythmic stimulus to which all organisms including the first protocells had to adapt and respond. This adaptation is seen in the form of molecular clocks present in every cell - optimizing every function to a specific time of the day. In the case of glucose metabolism, the liver is regulated such that it stores glycogen in the day from our glucose intake, while at night it breaks down the same glycogen to glucose (because we don’t eat at night). Lifestyle changes contribute to metabolic disorders and I wish to understand the mechanism behind this, for which I am connecting organs of various sizes and functions like the hypothalamus, pituitary gland, adrenal gland and liver. The study of these inter systemic interactions are computationally within the reach because it allows us to make some minor assumptions at some places to predict the outcomes of scientific scenarios which are difficult to recreate. To sum up, the computation can solve the questions of evolution, but the accuracy we could achieve is highly debatable.

9. What was the motivation behind your dissertation work which deals with circadian rhythm?

I had this problem statement in my mind for about a year before I started working on it. Ashok sir motivated his students in the Systems Biology course to give frequent presentations on scientific problems. While looking for information to present on circadian rhythm, I came across a video lecture by Dr. Michael Rosbash, who had won the Nobel prize for discovering the molecular clock circuitry. In the video, he explained about the peripheral clocks present in our body and how they are entrained with one another and regulate physiological processes. This pushed me to work on it and I thought that my mini-project would be the perfect platform to start my work.

10. Any words of advice to your juniors?

One thing that I have observed during my time at SASTRA is, books only help you to grasp the basics of any field. To delve deep into the field, you must try picking up on a problem statement, analyze the problem and study the scientific methods with which people have tried solving similar problems. During this process, you would eventually arrive at ways by which you could solve your problem. Choose the solution which would be the most optimal for your problem. This type of trial-and-error approach would seem like a long shot and a much smaller step in learning. Science is so vast that you need more than a lifetime to learn everything. Therefore, I would suggest the above approach irrespective of whether you prefer computational biology or not. My personal experience has taught me this approach and it offered me clarity and understanding deeper than what I would have gained by reading books.

Another learning experience from BCMR’s philosophy was - ‘Growth happens only when you push yourself outside your comfort zone’. Applying this principle has given me some of the best experiences including participation in iGEM’s Entrepreneurship program and the inception of the online platform of Chat de Science.

I would also advise my juniors to not undermine any other source of information, keeping research articles at the helm. I would emphasize the fact that visual cues help us understand some concepts more efficiently and info series and videos do help in this process. There are also a plethora of online courses offering the best of knowledge, which are a tap away from being accessed. So, make good use of them to understand and enjoy the beauty of science!

Team In Vivo wishes Swetha the very best for her future endeavors!