Origins and evolution: My interdisciplinary research journey in India

My research journey has been very thrilling, as I was introduced to different scientific disciplines right from the beginning. It started with my MSc degree in Biotechnology at Indian Institute of Technology Bombay, Mumbai where I completed my thesis on bioinformatics with P V Balaji. Simultaneously, I worked on a biochemistry-related project as a Visiting Student Research Programme student at the Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, under the supervision of Shobhona Sharma. Being an experimentalist at heart, I started to look for an experimental lab for my PhD even though my master’s thesis was in comparative genomics. Fortunately, I secured a PhD position in Andres Jäschke​’s Bioorganic Chemistry lab at Heidelberg University, Germany.

Here, I was introduced to research on the Origins of Life which significantly shaped my future career.

Like many, I too was fascinated with outer space and wished to be an astronaut but always felt that space research was outside my area of expertise. As I began my PhD, I discovered that space research is a big umbrella that brings different disciplines together to address the many mysteries of outer space including questions surrounding the Origins of Life. The National Aeronautics and Space Administration (NASA) was supporting a large Astrobiology programme, which included research on RNA evolution. I was on the right track! 

My PhD centred on the ​‘RNA World’ concept, which posited an era in the origins of life on Earth where RNA stored information and had catalytic functions. I concentrated on evolving RNA enzymes (called ribozymes) and in vitro using directed evolution methods. Additionally, I learned new skill sets like basic chemical synthesis, chemical labelling of RNA, and peptide synthesis that proved useful later. 

Shifting gears…

Until now, I had made a relatively small shift from genomics to a bio-organic lab. My PhD had led me towards the intersection of different disciplines and Origins of Life studies. Afterwards, I moved to Paris for my postdoctoral research at ESPCI Paris, where Marie Curie discovered radioactivity and several other Nobel Laureates had worked. Though the lab focused on single-cell genomics and antibody discovery, I joined an Origin of Life project based on RNA self-replication in water-in-oil emulsions. This helped me develop a broader perspective about Origins of Life research and at the same time learn new skills. I analysed self-replicating RNA network dynamics and their evolutionary potential using droplet-based microfluidics and single-droplet sequencing.

One of the most intriguing things about the lab was that one of my mentors was a physicist, Philippe Nghe, and the other was a biochemist, Andrew Griffiths. This combination made me adept at approaching research problems from a quantitative perspective and combining theory with experiments. By attending symposia and brainstorming sessions, I had the chance to collaborate with other theoretical groups.

Moving back to India…

The exposure in Paris paved the path for my next career steps. While I was thinking of returning to India, it was clear that setting up an ​‘Origin of Life’ lab in India would be a daunting challenge. At times, I was also discouraged from working on such an abstract topic, which had little translational potential, at an early stage of my career as there would be less support. 

However, in the last year of my postdoc, an opportunity at the National Centre for Biological Sciences (NCBS) struck me. NCBS has a Campus Fellow programme where you bring your ideas and look for a lab to host you. In 2019, I became an independent campus fellow hosted by the Simons Centre for the Study of Living Machines at NCBS to set up work on RNA network evolution with Shashi Thutupalli (experimental lab) and Sandeep Krishna (theory lab). 

Since the Thutupalli lab was working on soft-matter physics and had a strong interest in Origin of Life studies, together with Shashi and Manoj Kumar, a fellow postdoc, I analysed RNA networks inside liquid-liquid phase-separated (LLPS) droplets, a model proto-cell system. During my time at NCBS, I was captivated by these membrane-less phase-separated droplets but realised that several fundamental questions need a quantitative understanding, especially in the context of structured and functional RNAs. We further explored the dynamics of oligonucleotides inside the constrained microenvironment of LLPS droplets with Anupam Singh, a PhD student in the lab. 

Thanks to NCBS and Simons Centre, the fellowship turned out to be a perfect opportunity to move back to India and pursue my Origin of Life research. At the same time, it proved useful in adapting to India’s research ecosystem and applying for faculty positions. 

Starting my group…

Multiple encounters over the years with various individuals, their mentorship, and exposure to different fields have opened my eyes, moulded my perspective, and equipped me to operate at the intersection of various disciplines. The next step was to start my research group. After several applications, I got a faculty position offer from Ashoka University in the Department of Biology, Trivedi School of Biosciences to set up the Functional RNA Lab.

I realised that they share the same excitement and passion as I have for Origins of Life research.

Ashoka has a diverse mix of researchers and experts – a vibrant environment to carry out cutting-edge research and teaching. Different disciplines are intertwined, giving an ideal atmosphere for me to address the research problems of my interest. Currently, the lab is focusing on developing synthetic chemical systems that can evolve, with an overarching goal of constructing ​‘life-like’ chemical systems. At the same time, we are also analysing the dynamics of functional RNAs in the complex microenvironment of LLPS droplets. In addition, as I am always excited about RNA evolution, we are also evolving novel RNAs using machine-learning algorithms. 

While I have dealt with several challenges over the years, there are still many obstacles to overcome, such as obtaining adequate funding for this fundamental research programme and attracting a steady stream of students eager to immerse themselves in this fascinating but demanding work. Nonetheless, the future is bright. With the support of mentors and friends, we are constantly trying to develop a sustaining pedagogic and research programme centred around the emergence of life on Earth and other planets.