Genome-wide impact of oscillatory dynamics in gene expression during development and stress

• Applicant: Nicolas Battich, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546015003

Transcriptional oscillations are a fundamental feature of gene expression in different cellular processes, including differentiation and the response to genomic stress. For example, during early embryogenesis oscillations driven by the so-called segmentation clock result in the formation of somites. Likewise, the p53-Mdm2 negative feedback loop initiates oscillations as a response to genomic stress caused by ionising radiation. However, the extent to which transcriptional oscillations propagate from nascent to mature RNA and throughout the genome under the control of complex gene regulatory networks (GRN) remain poorly understood, both in the context of development and genomic stress. Furthermore, how parameters such as the RNA nuclear export rate and the degradation rate constrains the propagation of oscillations is unknown. In addition, it is unclear how different oscillation phases are generated by the respective GRN, especially since hundreds of genes, which oscillate in different phases are involved in these processes. In this project, we aim to develop a new strategy to address these open questions based on time-resolved single-cell RNA sequencing to 1) detect regulated transcriptional oscillations and distinguish them from stochastic cell-to-cell variability and 2) study how the oscillation generated by the core molecular regulators are spread through the genome by GRNs. This will include assessing the parameters that constrain propagations from nascent to mature mRNA, as well as determining how distinct GRN create distinct oscillatory phases during genomic stress and human somitogenesis. In summary, the project is set to uncover common characteristics in and parameters for the regulation and propagation of controlled transcriptional oscillations in complex human cellular systems.

• DFG Programme: Research Grants
• Major Instrumentation: Microfluidic Platform for Single Cell-Omics
• Instrumentation Group: 3190 Sonstige Geräte der Klinischen Chemie und Molekularbiologie