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BE: Seminar, Mechanonucleargenomics
March 6 @ 4:00 pm - 5:00 pm
Speaker: Kundan Sengupta
Title: Mechanonucleargenomics
Abstract: It is well established that chromosomes occupy a unique sub-volume in the interphase nucleus referred to as Chromosome Territories. Remarkably, chromosome territories are organized in a non-random manner with gene rich chromosome territories toward the center and gene poor chromosome territories proximal to the nuclear border. What are the molecular mechanisms that organize chromosome territories in a non-random manner in the nucleus? To address this question, we subjected cells to softer hydrogels with stiffness ranging from ~2 to ~55 kPa, while collagen coated glass coverslips (~1 GPa) served as reference. Cells exposed to softer substrates, showed an increase in surface area, over time.
Furthermore, transcriptomic analyses involving RNA-Seq revealed a strikingly altered transcriptome. Interestingly, cells on softer matrices also showed a significantly altered configuration in the otherwise highly invariant locations of chromosome territories. Remarkably, nuclear envelope proteins – lamins and LINC (linker of nucleoskeleton and cytoskeleton) complex, mislocalized into the nuclear interior. Interestingly, the nuclear organization of active and inactive histone marks was also altered along with the activation of Emerin phosphorylation – the inhibition of which attenuated the relay of mechanochemical signals into the nucleus, abrogating the movement of chromosome territories in cells exposed to softer matrices. Taken together, our studies highlight a remarkable plasticity, adaptability and resilience of the nucleus to counter and protect genome organization and function from external mechanical forces.
About the Speaker: Kundan Sengupta completed BSc, MSc from Bangalore University. PhD from TIFR, Mumbai. Postdoc from NCI/NIH. Currently, Dr. Kundan is a faculty at IISER-Pune.