Changing fields after PhD, though possible, is not an easy decision to make. But thats what a PhD is all about, going out of your comfort zone !

Bhavana Muralidharan, our next pathbreaker, Principal Investigator and Neuroscientist at the Institute of Stem Cell Science and Regenerative Medicine, studies the region of the brain involved in higher order functions such as learning, memory, thinking, language and consciousness – called the cerebral cortex.

Bhavana talks to the  Shyam Krishnamurthy from The Interview portal about doing her PhD in molecular biology and taking on the challenge of doing a postdoc in the field of Neuroscience, driven by a long-standing fascination and scientific quest to understand the human brain.

For students, research not only teaches you to think in depth but also inculcates in you the perseverance and patience to adapt to new challenges !

Bhavana, can you tell us about your background?

I was born and brought up in Delhi. I belong to a middle class Tamilian family. My mother was a school teacher and headmistress and my father had his own small-time business. I did my schooling from Delhi Tamil Education Association (D.T.E.A) where I studied Science with Biology as a major in school.

I dabbled in a lot of extracurricular activities during school and college. I am a trained Bharatanatyam dancer. I participated in debates, elocutions and recitations competitions. These experiences played a pivotal role in shaping my personality, communication skills and ability to work in a team. Though I was curious during my early childhood, I was not really sure of what I wanted to do when I grew up. Like every other Class 11th student, I prepped for medical and engineering entrance exams. I wanted to be a doctor but could not clear the entrance tests. Biotechnology, then an upcoming branch, seemed like the closest match to my interest in becoming a doctor as I could become a scientist and spend my time doing medical research. 

What did you do for graduation/post graduation? 

I did B.Tech and M.Tech in Biotechnology from Guru Gobind Singh Indraprastha University. The coursework was a nice mix of technology as well as basic and applied biology, hence giving me an all-round exposure in understanding the ambit of biomedical science.

Tell us, what were the drivers that led you to such an offbeat, unconventional and unique career?

My mother was a pillar of strength and a huge inspiration during my growing up years. Having never attended college herself, she instilled in me the need for education, not simply as a means to earn money but also to use it as a tool to serve the society and in turn become a better person. 

The primary motivation was to be in the field of medicine/biology and contribute in an indirect way to patients by helping further our understanding of biomedical science by the way of research.

My school teacher Mrs Vasumathy taught biology in the most lucid way and created a deep interest in biology which made me appreciate the complexities and intricacies of the biological system all the way from the cellular level to tissues, organs and the whole organism level. This left a deep mark in me to try and understand this complexity 

I heard Prof Kannan, Dean of my B.Tech/M.Tech programme echo similar sentiments during the admission counseling. He talked about how both fundamental and application research have created new drugs, molecules and therapies for patients. He talked about the manufacture of insulin, erythropoietin and stem cells, and their potential applications. 

All these events were instrumental in me choosing to be a scientist in the biomedical field.

How did you plan the steps to get into the career you wanted? Or how did you make a transition to a new career? Tell us about your career path

As I progressed towards the end of my B.Tech, I was more or less sure that I wanted to be a researcher in the field of biomedical sciences and hence wanted to get a first hand experience of research. I did my dissertation in the field of stem cell biology. This was a 6 month project which involved reading research papers to understand more about the field – past , present and the future. Based on the study of the literature we had to make a hypothesis and design experiments, execute and troubleshoot them. Overall, this training created a curiosity in me to do a PhD in Biology to explore a particular topic in depth. Thereafter I went on to secure funding from the Council for Scientific and Industrial research ( CSIR) to undertake PhD in India. I was also selected by the National Centre for Cell Science to do a PhD there. I began my PhD at NCCS under Dr Vasudevan Seshadri in the field of molecular biology to study how insulin is produced in the body upon glucose stimulation.

PhD taught me how to think in depth. It also taught me perseverance and patience because each experiment would take several days or weeks to finish and would not always be successful. This meant re-working the hypothesis or troubleshooting the technical aspects of the experiment to make it work which would require long hours of benchwork and reading. 

In the end, I successfully completed my PhD with 2 first author papers. I switched fields to do a postdoc in the field of Neuroscience. I was always curious about the brain and was fascinated to study the inner workings of the brain. 

Changing fields after PhD, though possible, is not an easy decision to make and would require going out of one’s comfort zone. I wanted my science to have leanings to a more clinical or application-based research and decided that studying brain and its development would be a very good starting point. 

I started my Postdoc in the lab of Prof Shubha Tole at TIFR in the field of study of the development of the nervous system. 

Prof Shubha was looking to hire a molecular biologist and I took on the challenge of developing molecular biology techniques undeveloped in the lab and in the process learn neurodevelopment.

Here I secured a very prestigious and competitive fellowship called the Wellcome trust/ DBT India Alliance fellowship awarded to postdocs/early career researchers to perform research under the mentorship of a principal investigator and to embark on the journey to become an independent researcher.

The India Alliance highly encourages researchers to move fields and saw a huge potential in my application and decided to fund me.

A long-standing, deeply mysterious and fascinating scientific quest is to understand the human brain- the organ which helps us perceive, understand and navigate the world around us. 

The turn of the twenty first century saw huge advances in the field of neuroscience and the field is poised to explode in the next 50 years. The brain has a billion neurons (firing cells in the brain) and trillions of glia (support cells in the brain). All these cells are derived from a common pool of stem cells during development. How the various classes of neural cells are derived and how they connect with one another to make a functional circuit which leads to behavior is an intriguing question in neuroscience and I was very much taken up by it. 

Prof Shubha was a great mentor and helped me gain confidence and independence conducting research in Neuroscience. 

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two middle-age debilitating neurodegenerative diseases with no cure yet. To further gain experience into clinical research, I joined the lab of Prof Adrian Isaacs at the UK Dementia research Institute and worked on understanding the disease pathology of ALS and FTD by utilizing patient-derived induced pluripotent stem cells (iPSCs) and to devise novel therapeutic strategies based on CRISPR-Cas system to ameliorate the disease.

Thereafter I applied to the Institute of Stem Cell Science and Regenerative Medicine and started my independent research career as an Assistant Investigator. I work here currently with a lab of 6 members and with competitive and prestigious grant fundings from the Department of Biotechnology, Department of Science and technology and the DBT/Wellcome Trust India Alliance. 

How did you get your first break? 

Networking with colleagues in the institute, outside of the institute in India and internationally is very crucial as it is the foundation of research i.e. forging collaborations. Regularly attending conferences, meetings and symposiums in India and abroad helps in presenting one’s research work to scientists worldwide in your respective fields as well as hearing the latest research work from pioneers in the field which also aids in formulating new ideas. 

With competitive and flexible funding like the India Alliance fellowship, I could travel to national and international conferences easily without much thought about the costs, and network with my peers. This networking helped in improving my scientific knowledge and making contacts for faculty job positions.

What were some of the challenges you faced? How did you address them?

There are several day to day challenges associated with being a scientist. I think the biggest challenge is to motivate oneself and one’s lab members on challenging days when an experiment fails.

Perseverance, hard work, fortitude and passion for what we do is what keeps us motivated. Of course, we are suitably rewarded when our experiments work and our hypothesis is validated.

The other challenge is to keep a work-life balance because research requires one to work on weekends sometimes. We maintain cerebral organoid cultures which require a medium change during the weekend to keep them growing. One needs to cultivate hobbies or extracurricular activities apart from the work. This replenishes us from time to time to be able to give our best to research. I like to run and play badminton and spend my weekend playing badminton with friends.

Where do you work now? What problems do you solve?

I am presently a Neuroscientist at the Institute of Stem Cell Science and Regenerative Medicine (inStem). 

My lab studies the details of how the brain is made from scratch. Our study focuses on a region of the brain involved in higher order functions such as learning, memory, thinking, language and consciousness – called the cerebral cortex. We study how the different neurons (firing cells in the brain) and the glia ( support cells) are made from a pool of mother cells called stem cells. We also study how this process goes wrong in neurodevelopmental disorders such as intellectual disability, schizophrenia and bipolar disorder.

What are the skills required for your role?

My work requires highly specialised skills sets which have been acquired over a period of 15 years. To name a few, we perform sectioning of mouse brains sections to observe the different brain regions, we culture human neural stem cells and neurons from patient-derived induced pluripotent stem cells (iPSCs), we perform cell and molecular biology experiments. Some soft skills required include reading and assimilating research papers, and thinking and designing experiments.

What is a typical day like?

A typical day when I was a PhD student or PostDoc would involve doing experiments, reading papers, attending talks, discussing science with lab mates and my boss. Now that I am a PI, I have additional responsibilities. I still like to be at the bench and do experiments, especially since I am currently teaching and mentoring younger colleagues. I demonstrate and perform the experiments myself to show them the first time. I also teach courses to incoming graduate students. A lot of my time is spent on writing grants to secure funds for the lab. I am also involved in reviewing research articles for publication. 

During Covid time I helped run the Covid testing centre at InStem. This involved managing the RNA extraction team and ensuring timely delivery of the test results to anxious patients. 

What do you love about this job?

What I love about my job is that it lets me use my creativity and intelligence to ask and answer interesting and relevant questions in brain development and neurological disorders. I also love the independence and flexibility it provides to do my own thing. I love interacting with younger colleagues and my job gives ample opportunity to teach and learn from them. 

How does your work benefit society?

Science helps us understand the world around us so that we are better equipped to live a wholesome life. 

My work helps us understand brain development and what goes wrong in the process of brain disorders. Our research work will contribute in a small way towards our understanding of the human brain and its workings. 

Tell us an example of a specific memorable work you did that is very close to you!

My first paper from my postdoc is very memorable because I had switched fields and neuroscience was very new to me. The paper gave me confidence that I could perform neuroscience research and gave me the confidence to make a mark in this field. 

Your advice to students based on your experience?

There is no shortcut to hard work. It is the key. Patience and tenacity are also important if one wants to pursue a research career. Of course, I cannot overemphasize the need for work-life balance because the chances of burnout are very high and one needs to step away from work regularly to come back rejuvenated. 

Future Plans?

I hope to contribute towards understanding human brain development and what goes wrong in brain disorders. With this knowledge, we hope to design therapeutic strategies to treat brain diseases.