Department of
Biology

Ashish joined the Department of Biology, IISER Pune in February 2026 as a DST-INSPIRE Faculty Fellow. He received his PhD from Biomedical Center, Ludwig Maximilians University of Munich, Germany for investigating mechanisms regulating chromatin organization and its functions in budding yeast. For his postdoctoral training in the Department of Developmental and Stem Cell Biology at Institute Pasteur, Paris, he switched fields and established a quantitative method to map positive DNA supercoiling in mouse embryonic stem cells and investigated mechanisms driving its biogenesis.

Research

Mechanisms and functions of positive DNA supercoiling in development and disease

Genomic DNA experiences constant torsional stress generated throughout the cell cycle, primarily established by DNA strand separation during transcription and replication. As polymerases translocate along DNA, they induce overwinding ahead of the polymerase fork, producing positive DNA supercoiling. Simultaneously, DNA behind the polymerase becomes underwound, resulting in negative DNA supercoiling. Both positive and negative DNA supercoiling plays a critical role in regulating fundamental DNA transactions, including transcription initiation and elongation, replication fork progression, formation of DNA loops, three-dimensional genome organization, and mitotic chromosome condensation.

While several psoralen-based methods have been developed to characterize negative DNA supercoiling, positive DNA supercoiling remains entirely understood due to the lack of a suitable method, especially in higher eukaryotes. To address this limitation, we adapted the bacterial protein GapR, recently shown to recognize positive DNA supercoils in bacteria and yeast, to develop an inducible and quantitative approach for mapping positive DNA supercoiling in mouse embryonic stem cells across the cell cycle. We combine GapR-based profiling approaches with high-throughput genomic techniques including ChIP-seq, CUT&Tag, RNA-seq, ATAC-seq, TT-seq and MNase-seq together with their associated bioinformatic approaches.

The overarching aim of the lab is to understand the mechanisms that drive the establishment and resolution of positive DNA supercoiling and to determine how these processes influence chromatin dynamics, genome organization, and cellular functions during the cell cycle.