Fundamental research, though laborious, gives you the skills to handle the unknown while engaging in the thrill of new and cutting edge discoveries!

Rashmi Tripathi, our next pathbreaker, works independently as part of ConLifeSci, performing scientific research in the areas of human health using high throughput computational technologies.

Rashmi talks to Shyam Krishnamurthy from The Interview Portal about the awe-inspiring experience of working at the Wellcome Trust Sanger Institute in the United Kingdom, part of the public consortium that had sequenced nearly 25% of the human genome.

For students, computational technologies are giving researchers unparalleled insights into the workings of life processes. Take up a career in technology driven fundamental research !

Rashmi, tell us about your background?

I grew up across many cities in India. I was born in Delhi. My father worked in Baroda, Bangalore, Delhi and Chennai. I did my primary school in Delhi, middle school in Chennai and high school in Delhi again. My extra-curricular activities included sports such as badminton, tennis and volley ball; poetry recitation and art. I used to also write for our school magazine. My interest in biology was sparked by a discussion on genetics with my parents when I was very young. My curiosity regarding how genes worked led me to undertake Biology in Class XI along with Physics, Chemistry, Maths and English. This was quite different from the specialization of my parents. My late father was an Electrical Engineer from IIT Madras and my mother is a doctorate in political science from JNU. They have been my primary motivating factors giving me the freedom to pursue life on my own terms and always providing a listening ear when needed. 

What did you do for graduation/post graduation?

I was always more interested in fundamental science, never motivated to join the rat race in taking competitive exams for engineering or medicine. For me it was important to understand living systems at the deepest level. Hence I decided to study Microbiology at Delhi University. This course taught me so much about biochemistry, molecular biology, physiology and ecology besides focusing on the significance of microbes in medicine, industry and biotechnology. For my post graduation, I cracked multiple entrance tests for study in the best institutions such as JNU, IIT and AIIMS, but decided to go to the National University of Singapore (NUS) to study something very fundamental in biology-  protein-protein interactions between transcription factors. Although experiments were laborious, finding out something new in research, previously unknown to anyone, provided happiness and compensated for feelings of frustration and despair.

At NUS, I took an exciting course on genomics which was very new, given the human genome was sequenced only very recently. The lecturers infused their passion for the subject in me, motivating me to go to the Wellcome Trust Sanger Institute in the United Kingdom, part of the public consortium that had sequenced nearly 25% of the human genome. Here I decided to investigate a novel class of molecules called microRNAs in stem cell pluripotency and differentiation. I had the privilege to work with some of the best minds in science and learnt a lot in statistics, bioinformatics and genetic engineering. I obtained my M.Phil degree from Cambridge in 2009. Subsequently, I received the opportunity to continue with my Phd (Biotechnology) at Cambridge itself and graduated in 2012.  

What made you choose such an offbeat, unconventional and unique career?

My key influencers were my parents, friends in school and teachers.

I’ve had multiple mentors during school, college and post-graduate studies. I will not do justice by naming any specific person(s). 

When I was in school, I attended a lecture by Prof. Jim Watson, who made the pioneering discovery of the nature and structure of DNA. His lecture was truly inspirational. We also attended an exhibition on DNA, that led me to believe that my future would involve studying molecular biology. Listening to Prof. Paul Nurse in Delhi and learning about the cell cycle checkpoints also influenced my decision about gaining in depth knowledge in molecular biology.

One of the biggest turning points was studying genomics at NUS that led me to apply to Cambridge.  

Tell us about your career path

During my undergraduate studies I was fortunate to intern at C.B. Richard Ellis and Maulana Azad Medical College Virology department during my second and third year respectively. These internships provided experience which probably impressed my selection committees at NUS and Cambridge. At CB Richard Ellis, I learnt to use MS Excel for the first time performing data analysis for consultants. My experience at Maulana Azad Medical college was highly relevant to apply what I had learnt theoretically in the real world of viral diagnostics in a hospital setting. 

At NUS I worked part-time as a graduate student tutor and researcher. I really enjoyed teaching undergrads practical skills, since I felt I was making a real contribution to their lives positively.  I was also the recipient of many scholarships during my postgraduate studies at NUS and Cambridge.

I  worked briefly as a project assistant after my M.Phil at Cambridge in the Tunnacliffe lab at Cambridge, which was later also my Ph.D lab. I supported a postdoc studying the functions of late embryogenesis abundant (LEA) proteins in conferring desiccation tolerance in various organisms. 

My doctoral work characterized the intricacies of LEA proteins inside cells biophysically and biochemically. Obtaining microscopic, physiological and biochemical data to fill my thesis was a lot of fun. My research showed that LEA proteins traffic inside cells in a regulated manner and protect other proteins from the harmful effects of water loss that normally destroys the molecular fabric of cells. 

After my Ph.D, I decided to test whether LEA proteins could be used to alleviate protein dysfunction in cystic fibrosis, a genetic disease caused by a single mutation in the protein encoding sequence of cystic fibrosis transmembrane regulator (CFTR) gene. Hence began my first postdoc at INSERM, Brittany, in France in 2013. Thankfully my supervisor was very supportive and allowed a lot of freedom to designing and performing experiments. I also characterized another CFTR chaperone called calumenin. I was thrilled to receive the Cell Stress Society International Award for this work in the U.S. What was amazing was the fact that my abstract was chosen among hundreds in the competition.

I decided to leave France since I felt my French was not good enough for academia and I felt I could be more comfortable in an English speaking country. 

I collaborated with Harvard, Imperial College London and University of Washington on diverse projects such as cystic fibrosis diagnostics, air pollution mediated toxicity and protein design of stem cell regulators respectively. 

After that I started working with an N.G.O called Global Awakening Ideas & Actors to generate online content on social media sites. Our purpose is to increase global connectedness to solve problems using science and technology. I was also motivated to conceptualize my own start-up ConLifeSci  to deliver innovative solutions in life sciences. 

In 2017 I got the opportunity to visit the beautiful city of Prague as a postdoc at Charles University. My research aimed to understand protein evolution in the origin of life scenario approximately 4.5 billion years ago. I also got the opportunity to work briefly with NASA on astrobiology related topics.

I have continued my research in the origin of life field along with looking at RNA interference pathways to treat Covid-19 at ConLifeSci. 

How did you get your first break?

Getting through National University of Singapore was my first break. I worked hard to get a good GRE score and was fortunate to be selected.

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

Challenge 1: Biological research requires a lot of patience and trial and error to get the right results. It requires a lot of focus and dedication. 

Challenge 2: Handling criticism. It is best not to be sensitive and not take things too personally. 

Challenge 3: Being overworked. It is important to maintain a work-life balance.

Where do you work now? Tell us about your research

I am working independently as part of ConLifeSci. Past problems have included deciphering the evolution of the amino acid code in the origin of life scenario and elucidating the RNA interference molecules against Covid-19.

All my work has been computational so far using skills acquired at Cambridge and France. 

A typical day might involve running programs, writing programs and manuscripts. 

Working with the N.G.O and the start-up India initiative motivated me to try being an entrepreneur. The idea is to perform scientific research and development in the areas of human health. Initially I proposed increased milk intake to reduce air pollution toxicity. Other commercial ideas include developing high throughput diagnostics applying genomics. I’m also interested in RNA based therapies. I’m always open to performing blue skies research, with no immediate commercial implication but with useful insights for the scientific community, like my work on evolution of the amino acid code.

How does your work benefit society? 

Most of my work involves generation of biological knowledge that helps advance science. My research might also benefit cystic fibrosis patients in the future. I am also hopeful that RNA based therapies might one day cure numerous human diseases ranging from cancers to viral diseases.

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

My work in the area of cystic fibrosis in France is the closest to my heart. 

Cystic fibrosis is caused by a single point mutation in the gene encoding CFTR protein whose main function is to maintain ionic balance across cell membranes lining the airways and various other organs such as intestines, pancreas, testis etc. In the absence of normal function, the airways get clogged producing excess mucus and become a hot-bed of bacterial infections. Patients can have problems breathing and generally have a much reduced lifespan due to malfunctioning lungs and various other organs. My research elucidated the factors that affect CFTR folding and function. These results can help regulate its folding in the future and perhaps enhance its function biophysically, with implications in treating the disease.

Your advice to students based on your experience?

It’s important to have passion for any field of study or work you might undertake. Besides inspiration, ‘genius’ always involves a lot of perspiration! 

Future Plans?

I might undertake some more work in the industry or academia.