Nordic Life Science 1
36 “The prize is already beautiful as it is. They
uncovered a regulatory system that has important functions in most, if not all, cell types of our bodies, and generally in multicellular organisms.” W Rickard Sandberg, Professor, Department of Cell and Molecular Biology, Karolinska Institutet, and Member, the Nobel Assembly at Karolinska Institutet hen asked about exciting, future applications of microRNA, Sandberg emphasizes that he thinks that the prize is already beautiful as it is. “They uncovered a regulatory system that has important functions in most, if not all, cell types of our bodies, and generally in multicellular organisms,” he says. Sandberg and his colleagues are currently not directly focusing on microRNAs in their lab, but he actually did so during his postdoctoral period. “I studied how alternative polyadenylation site usage, e.g. after T cells gets activated, results in mRNAs with smaller 3’UTRs. This results in higher protein production since they can escape the microRNA mediated suppression,” he describes. Uncovering principles and mechanisms of gene regulation Rickard Sandberg’s lab at Karolinska Institutet focuses on uncovering the principles and mechanisms of gene regulation by developing strategies for more precise measurements of RNA in single cells. “We have recently found several principles explaining how transcriptional bursting is encoded in the regulatory DNA sequences, demonstrating the importance of promoter regions for burst sizes and enhancers for burst frequencies,” he explains. “Moreover, we have demonstrated that in genes that generate more RNA molecules per burst, the synthesis rate is higher whereas the time period of the burst stays the same. This teases out fundamental principles for transcriptional regulation and dynamics in cells,” he adds. S andberg and his colleagues are currently working on how alternative splicing is regulated across cell types in the brain to specify cellular functions. Despite great efforts to molecularly characterize the brain in the past decade, very little data exist on alternative splicing. “We would like to investigate the degree to which alternative splicing is used to diversify neuronal functions in the brain, e.g. molecular compatibilities between cell types and functional signal transmission through synapses. This has ramifications for understanding the extent to which neuronal wiring is hardwired by molecular cues, and gives better insights into disease progression, e.g. neurodegeneration and neuropsychiatry, that is intricately linked to splicing (or rather mis-splicing),” Sandberg explains. NLS THE NOBEL PRIZE // PHYSIOLOGY OR MEDICINE PHOTO JOHANNES FRANDSÉN