THIS MONTH to molecular biology, genomics and bioinformatics, also in relation to cancer biology. THE AUTHOR FILE On occasion “something unexpected” with commer- cial potential happens in the lab, says Balasubramanian. With his colleague, chemist David Klenerman, he Shankar developed ‘sequencing by synthesis’ with fluorescently labeled nucleotides and in 1998 formed the company Balasubramanian Solexa, which was acquired by Illumina in 2007. The A chemist intrigued by DNA and RNA structure technique is at the heart of Illumina’s high-throughput and two-wheeled mountainous ascents. sequencing. It has been gratifying to see population- scale whole-genome sequencing emerge. “Nearly 20 years on, that big vision is now playing out,” says Cambridge is a Balasubramanian. He also cofounded the epigenetics thought-provoking, tools company Cambridge Epigenetix. beautiful environment “I love doing science,” says Balasubramanian. “Still, with a close-knit com- as a scientist it is essential to have a life.” Doing things munity across all dis- outside of the lab keeps him balanced; it enhances ciplines, says Shankar reflection and stimulates creativity, he says. His wife and Balasubramanian, children are central to his life, and they all go on hiking a researcher at and cycling trips together. As a teenager he played many the University of sports, and he has recently taken on endurance running Cambridge who has and cycling. It keeps him fit and is a form of medita- appointments in the tion that helps him think.

University of Cambridge of University chemistry department He has cycled to the top of “I love doing and at the university’s Mont Ventoux, a challeng- science.” Cancer Research UK ing ascent even for Tour de Cambridge Institute. France cyclists. Chemists In this issue he publishes two papers, one of which in Cambridge are known to meet in a pub called The describes a technique to capture and sequence dou- Panton Arms, which, says Balasubramanian, has the ble-strand DNA breaks (DSBs) more robustly, sensi- right environment for relaxed, open and enjoyable tively and with greater precision, he says. conversation. “At a time when the culture of research is DSBCapture simplifies the preparation of sequenc- sometimes dominated by deadlines, paperwork, short- ing libraries used by researchers to study various types term measurables and competition, it is important to of DNA damage. The method will also help clarify the foster open discussion and a creative culture of ideas role of G-quadruplexes (G4s), which are four-stranded generation,” he says.

Nature America, Inc. All rights reserved. America, Inc. © 201 6 structures that can form in DNA. His interest in G4s led Balasubramanian says it’s good to consider many him to DSBCapture, says Balasubramanian. G4s appear ideas and reject most, even all of them, on think- to be located at sites where DSBs can occur, but these ing them through. Wolf Reik, a collaborator at the sites have been tough to map. Now G4s can be charac- Babraham Institute, says he loves discussions with his npg terized at higher resolution and in different cell states. friend and kindred spirit about new science ideas, espe- Balasubramanian and his team have also developed cially multidisciplinary approaches involving chemis- RNA G4 sequencing (rG4-seq) to profile these struc- try, molecular biology, and cutting-edge biology and tural motifs across the transcriptome. He hopes that medicine problems. “I think of Shankar as a mentor- rG4-seq will help scientists interrogate any collection musician,” says his former postdoctoral Yamuna of input RNAs to identify stable rG4s. “When applied Krishnan, now a University of Chicago professor. He across the transcriptomes of many organisms this will reminds her of a former neighbor learning to play the help us see whether there is generality in some of the recorder: one day the cacophony had become music. proposed roles of rG4s across species,” he says. The Balasubramanian did the same in the lab—“without scientists also believe that the regulation of some tran- us noticing he transformed the scientific cacophony in scripts may be modulated by the presence of rG4s in our minds into music,” she says. Conversations led to microRNA target sites. deep questions. Krishnan still struggles with his latest Balasubramanian completed his PhD in chem- one: given infinite money, what would be the one prob- istry at the and his post- lem you would solve? “His questions get tougher by the doctoral fellowship at Pennsylvania State University. year,” she says. He returned to Cambridge as a fellow, then became Vivien Marx a reader and ultimately was appointed professor in Lensing, S.V. et al. DSBCapture: in situ capture and 2007. His interests in the structure and function of sequencing of DNA breaks. Nat. Methods 13, 855–857 (2016). DNA and RNA are those of a “card-carrying chem- Kwok, C.K. et al. rG4-seq reveals widespread formation of ist,” he says. Over time his work expanded beyond the G-quadruplex structures in the human transcriptome. Nat. chemistry and molecular biophysics of nucleic acids Methods 13, 841–844 (2016).

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