I am the first graduate and scientist from my family. Growing up, I had relatively limited exposure and access to science. A career in academia was not even a distant dream! Nevertheless, my science teacher inspired me to take up science as a major after high school. Curiosity determined my subsequent choices, and despite many hardships along the way, here I am today! In retrospect, I am glad I was bold enough to pursue this unknown path, and I am acutely aware of the difficulties faced by students who come from underprivileged backgrounds because I come from the same.

My interests widened from bookish science to experimental research during my master’s degree, when I observed agarose gels displaying differential DNA amplicons from various mulberry species found in India. The differential DNA bands were the result of DNA base changes in those species. This fascinated me. How do single changes in the alphabet that makes up DNA (known as genetic variation) create phenotypic differences in a population? It was a humble start, but from this fascination grew my interest in gene regulation, driving me to pursue a PhD in gene regulation in India.

Gene regulation is a multifaceted phenomenon that involves the fine-tuned co-operation of many players — including transcription factors (TFs), histones and non-coding RNAs (ncRNAs) — on a genome, whose folding changes and which contains regulatory DNA elements. As a newcomer to the field, one can get lost if exposed to all these ideas simultaneously. I was exposed to these multiple facets in a stepwise manner, which allowed me to understand and appreciate these concepts deeply.

My PhD research in Sanjeev Galande’s lab, then at National Centre for Cell Science, Pune, was focused on the regulatory roles of a TF in gene regulation. During my postdoc in the laboratory of Michael G. (‘Geoff’) Rosenfeld at University of California San Diego, I was prepared to interrogate the complex gene regulation ‘cocktail’, where all gene regulatory components mentioned above function together towards a common goal of fine-tuning gene expression in a spatio-temporal manner.

By 2009, when I started my postdoc, next-generation sequencing had begun revolutionizing genomics, enabling the discovery of a plethora of genomic elements, including enhancers. However, their functional understanding was lacking. I took advantage of genomic techniques to first understand if disease-associated genetic variation within enhancers had any effect on target genes. We observed that a disease-risk allele located in an enhancer affected binding of a key transcription factor, which in turn changed how cells carrying that allele responded to activation of that transcription factor in terms of long-range enhancer interactions and expression of neighbouring genes. These results, for the first time, revealed how genetic variation in an enhancer can alter the disease susceptibility of a population or individual. The findings convinced me to pursue these important elements to better understand them, and I am still hooked. My second project in Geoff’s lab was to understand the functional role of enhancer-associated RNAs (eRNAs) as they had just been discovered but were perceived as ‘transcriptional noise’. By utilizing chromatin conformation assays and genome-wide mapping of nascent RNA synthesis in the context of oestrogen receptor-α activation, we revealed the direct role of eRNAs in signalling-induced gene transcription and enhancer–promoter contacts. In spite of the field’s intense focus on enhancers, our current knowledge of enhancers is just the tip of the iceberg. The unknowns continue to intrigue me and motivate me to pursue these fascinating regulatory elements in my laboratory.