Uncovering mechanisms of transcriptional regulation using advanced microcopy and computational analysis
The regulation of transcription is a fundamental process that mediates the development of multicellular organisms. Despite the inherent stochasticity of transcription, individual cells are able to reliably react to internal and external cues to adjust the activity of specific genes at defined time points leading to coordinated tissue organization and proper organism development.
In order to understand general concepts of transcriptional regulation it is often no longer sufficient to rely on single experiments. Instead, it is necessary to integrate measurements from various experiments created by technologies such as electron microscopy, light microscopy or sequencing into comprehensive models of development. Such measurements for example include gene expression profiles at cellular level, changes in mRNA and protein localization on cellular and subcellular level, transcription burst characteristics of genes, or neuronal activity patterns. For each measurement, these models are then able to capture the average behavior as well as its natural variability. Such powerful in-toto descriptions of developing organisms at single-cell and single-molecule level therefore allow to uncover unknown relationships in the data and enable to characterize the effect of mutations and disease at unprecedented accuracy, precision, and coverage. We develop technologies to acquire and reconstruct data with the necessary spatial and temporal resolution, to integrate data from many sources such as single-molecule imaging techniques or light-sheet microscopy, and to handle it efficiently. We apply these technologies to study mechanisms of transcriptional regulation underlying exit from the dauer stage and mechanisms of dosage compensation in C. elegans embryogenesis.
Start Lab in 2015