India’s cultural diversity is astounding, and so is its biological diversity; the geographical variation in venom composition within and across a snake species presents an incredible challenge to the development of anti-venom !
Diganta Das, our next pathbreaker, Postdoctoral Researcher at The Keck School of Medicine of University of Southern California, researches how cancer cells migrate or metastasize from breast to brain.
Diganta talks to Shyam Krishnamurthy from The Interview Portal about his PhD work on the Northeast Indian Cobra (Monocled Cobra) venom composition and identification of a novel neurotoxin from the snake which will help in understanding venom variation and pharmacologically important snake toxins.
For students, whether it is venom or cancer, we have barely scraped the surface of human physiology in terms of deciphering its intricacies and complexities!
Diganta, tell us about your growing up years?
I was born and grew up in a village called “Jalah” in Barpeta district of Assam, India. My father and mother used to work in the state Health Department as optometrist and nurse respectively. I studied in a primary government school in Jalah and later completed my schooling in Jawahar Navodaya Vidyalaya in Barpeta. Though I was good in biology from my school days, in the beginning I was very much confused about choosing a career between medicine and biotechnology. Later my private teacher in school influenced me to opt for biotechnology as a career.
My father and mother always used to encourage extracurricular activities, be it games or art. I was very interested in music and learnt various traditional art forms. I learned Assamese ‘Sankari’ traditional ‘Bhortal Nritya’ (devotional dance form), played ‘Khol’ (a devotional membrane instrument), Tabla, sang ‘Borgeet’ (Assamese devotional songs) written by ‘Mahapurush Srimanta Sankardeva’ and his disciple Madhabdeva, as well as other Assamese & Hindi songs. Later, I self-taught myself how to play the acoustic guitar.
What did you do for graduation/post graduation?
I did Bachelor’s in Biotechnology and Master’s in Biochemistry from Bangalore University and PhD in Molecular Biology and Biotechnology from Tezpur Central University in Assam, India.
What were some of the influences that prompted you to pursue such an offbeat, unconventional and unique career?
It was my private teacher in high school who initiated my interest in biotechnology as a career. However, back in 2003, biotechnology courses were very limited in universities across Assam. Therefore, I decided to move to Bangalore, Karnataka for further studies. Most importantly, my father and mother always had faith in me and relentlessly supported and motivated me to do good. They have always been my key influencers and mentors. I consider my decision to join Master’s in Biochemistry as a turning point in my career.
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
Biotechnology is a broad term with multiple subjects included under it, and therefore although I successfully completed BSc Biotechnology program, I again found myself in a dilemma. This was the point when I actually looked towards the outer world and tried to understand what a practical step would be to pursue a career in Biotechnology. I decided not to merely follow a general trend of completing a masters. I connected and shared my thoughts with my seniors, professors, and friends of friends from top institutes from India and abroad and took at least 2-3 months to decide my next step. I finally decided to pursue a Master’s in Biochemistry although I was comparatively weak in Biochemistry. I took on the challenge and later on, the core biochemistry subjects such as protein chemistry, enzymology became my favorites. Additionally, human physiology was one of my top interests. It was very interesting to connect subjects, find a correlation and figure out what is the actual objective of learning different subjects. Until graduation, though I used to learn only a particular subject, during my masters I learned to connect them as well.
I was selected for a PhD program in Tezpur Central University in Tezpur, Assam. Though I have always been interested in proteins, working with snake venom proteins was an exceptional experience. My research on snake venom was a blend of field and bench work. To do snake venom research we can either buy snake venom from firms like Irula in Tamilnadu who are one of the pioneers in supplying the venom of the Big Four snakes (Spectacled Cobra, Russell’s Viper, Saw Scaled Viper, and the Common Krait) or legally collect venom samples ourselves after satisfactory training. My PhD project was on the Monocled Cobra from Assam where I reported venom composition, purification of a 3FTx and biological characterization. Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes.
We also wanted to address the efficacy of the commercially available antivenom in neutralizing the Monocled Cobra venom of Northeast India. This was very important since the commercially available antivenom in India is raised from the ‘Big Four’ venom (the Big Four is considered responsible for majority of the fatal bites across the country), however geographical variation in venom composition within and across a snake species is common, for example monocled cobra is very common throughout Northeast India instead of spectacled cobra, likewise banded krait is more common than common krait. In both the cases, the genus (it’s a taxonomic group covering more than one species) is different and can be a major factor for variation in venom composition. Now, when a snakebite victim in Northeast India visits a hospital, the patient is administered with the Big Four antivenom. I think this makes the situation even more complicated since antivenom has multiple side effects and possible neutralization inefficiency against a geographically different venom.
Altogether, my PhD journey was very exciting since I was working on something never reported from our region. My PhD work reports on the venom composition, purification of a non-conventional three finger toxin and biological characterization of monocled cobra from Northeast India. Along with my core project, I was also associated with other venom related projects on Big Four venom. I was offered a DBT fellowship to pursue my PhD.
Soon after my PhD thesis submission, I got associated with an NGO (Balipara Tract and Frontier Foundation, Balipara, Tezpur, Assam) and joined as a project consultant/manager. I got funded by the private sector for a project that I submitted and worked as a principal investigator. This was the beginning of my professional career. The project was based on snakebite management, public awareness on snakes and conservation. I used to organize meetings, find snakebite prone zones, record types of bites and deliver lectures on snakes and snakebite management across the district including the defense personnel. This project was the result of my understanding of snakes, venom composition differences and antivenom complexities. Although it wasn’t a direct application of my PhD project, I was closely working with medical personnel who are the primary care responders for snakebite victims. This helped me in understanding the current situation and gaps between research and clinical application in snakebite research and finding the dots to fill.
Meanwhile, I also applied to the DBT research associate fellowship program and was selected. Therefore, I left the NGO job and joined Indian Institute of Science, Bangalore as a DBT RA (Research Associate) for higher studies and research. My work in IISc didn’t change drastically from my PhD project, however I had the chance to work with different snake venoms across India as well as with venom from cone snails. I also got an opportunity to connect with many top-notch scientists both nationally and internationally. During my tenure in IISc, I was invited to talk on snake venom, snakes and snakebite management at various places in India. Most calls were from the NTPCs (National Thermal Power Corporation Limited), where they had serious snakebite cases. My lectures included snake identification (medically significant/ non-significant), venom, antivenom, dos & don’ts in a snakebite.
However, I was looking forward to broadening my research area and therefore I wanted to leverage my interests in human physiology and molecular biology. Cancer biology was one of the top priorities in my mind where I could utilize all my experience in proteomics and protein biology. To learn more, I used to connect to researchers around the world and share my interests. I did not have specific contacts or people whom I knew, instead I made connections and shared my experiences.
I was offered postdoctoral positions in the UK and USA and finally joined as a postdoctoral scientist at the University of Southern California, USA. I am currently working there, and my project is based on cancer metastasis from the breast to brain. This position has helped me in learning newer techniques, understanding and learning high throughput technologies.
How did you get your first break?
I consider cracking my JNV school entrance exam as my first break in my career.
What were some of the challenges you faced? How did you address them?
Challenge 1: Struggle for Proper Guidance
My interest in biotechnology was seeded by my private teacher, however nurturing that interest was very tough. During graduation, my idea of biotechnology as a career was blurry, and I think this is very common in many students. Although I was immensely interested, I lacked proper guidance. I tried to connect to seniors and senior professors to understand more and shape my career.
Challenge 2: Financial
Our family had a tough financial situation and at the same time I was selected in a MS program in cancer research in the UK. Even though I was offered a 50% discount in tuition fees and housing, we could not afford it. In the meantime, I qualified for the PhD entrance and interview in Tezpur University and additionally offered DBT fellowship to pursue research.
Challenge 3: Family Health
While I was in IISc Bangalore, my mother was seriously ill, and I had to spend 3-4 months in the hospital. Interestingly, during that time, I received postdoctoral offers from UK, Ireland and Cleveland in the USA but could not reciprocate. At the same time, I had to maintain my research in IISc. In those 4 months, I used to give at least an hour or two to work for my research while being in the hospital or while travelling. Though it was tough, it was responsibility and management on both ends.
Where do you work now? What problems do you solve?
I currently work at the University of Southern California, USA. We are trying to understand how cancer cells migrate or metastasize from breast to brain.
Can you explain how you are able to apply your expertise in snake venom biology to cancer biology?
Cancer metastasis can be correlated with snake venom spread throughout the victim’s physiology. Interestingly, whether it is cancer or venom, in both the cases, the carrier is blood. If we closely analyze, the major enzymes and proteins in these situations are similar and my transition from snake venom to cancer metastasis was perfectly in line.
What skills are needed for your role? How did you acquire the skills?
The most important skills required in my current work are planning and analysis. In terms of techniques, experience in cell culture, fluorescence activated cell sorting or FACS, confocal microscopy, RNA sequencing and animal handling are the most desired. I also have good experience in various chromatographic techniques for protein purification and characterization. Acquiring these skills is always a stepwise process and it takes time. Technical skills are very important and are a part of our experience right from the start of science practicals from schools. Most importantly, graduation and post-graduation courses and the associated dissertation works were the milestones. Later, the PhD course and subsequent experiences in my career added high throughput techniques.
My working day is planned the day before. It can be bench work or data analysis based on the schedule.
The interesting part in my current work is that I could connect everything I do for human wellbeing. Cancer is a dreadful disease and currently has very limited care when it comes to brain metastasis. By defining a pathway of how cancer cells migrate through blood brain barriers we will be able to identify therapeutic targets which will eventually help in its treatment.
How does your work benefit society?
My PhD project on the Northeast Indian Cobra venom composition and identification of a novel neurotoxin from the snake was the first report, which will surely help in understanding venom variation and pharmacologically important snake toxins.
Secondly, as the global incidence of cancer has increased, brain metastases now appear in 8-10% of all cases. In my current work, our goal is to study breast cancer and its ultimate metastasis to the brain from the perspective of the brain. I hope one day we will be able to decipher the path and molecular mechanisms associated with brain metastasis.
Tell us an example of a specific memorable work you did that is very close to you!
My first report of Northeast Indian cobra venom and purification of a non-conventional neurotoxin from the venom mixture was my most memorable project. This purified toxin was found to affect nerve conduction velocity in animals. The complete work is the first report from my region in India.
Your advice to students based on your experience?
The most important thing I have learned in my career is, if you want to do and achieve something in life you will have to give time to it and while investing that time you should feel happy and accomplished. Everyone is good and everyone can do their best, the toughest part is to figure out what you are good at.
I would like to be associated with research and after retirement me and my wife have plans to open a free school and teach students who are underprivileged in Assam, India.