Goal: Our research focuses on developing and using single-cell genomics to discover regulatory logic and mechanisms of gene expression. Single-cell transcriptomics enable transcriptional processes to be studied transcriptome-wide and with allelic resolution, providing a rich output for functional studies of transcription factors and co-factors regulating transcription.
Technology: Towards this goal, we have recently developed Smart-seq3 that provides sensitive profiling of RNAs in cells and importantly RNA reconstruction strategy that can directly link counted RNAs to allelic origin and transcript isoforms. Additionally, using 4sU labeling of newly transcribed RNA (e.g. NASC-seq) we can monitor transcriptional dynamics at precise temporal resolution.
Biology: Using these methods, we have demonstrated that most mammalian genes are expressed in bursts, where, as a first approximation, enhancer activities control burst frequencies and core promoter elements control burst sizes (Larsson et al. Nature 2019).
Still lots to be uncovered here, please join our efforts!
Interested students or postdoc candidates, please email me at rickard dot sandberg at ki.se