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Reverse mathematical methods for reconstructing molecular dynamics in single cell

Decoding the mechanism of transcriptional regulation from nascent RNA measurements

speaker: Sandeep Choubey (Max Planck Institute for the Physics of Complex Systems)

abstract: Cells constantly face environmental challenges and deal with them by changing their gene expression patterns. They make decisions regarding which genes to express and which genes not to express based on intra-cellular and environmental cues. These decisions are often made by regulating the process of transcription. While the identities of the different molecules that take part in regulating transcription have been determined for a number of different genes, their dynamics inside the cell are still poorly understood. The development of novel single-cell sequencing and imaging techniques, as well as a better exploitation of currently available single-molecule imaging techniques, provides an avenue to interrogate the process of transcription and its dynamics in cells by quantifying the number of RNA polymerases engaged in the transcription of a gene (or equivalently the number of nascent RNAs) at a given moment in time as well as a function of time. In this talk, I will demonstrate that measurements of the cell-to-cell variability in the number of nascent RNAs provide a probe for deciphering mechanisms of transcription initiation in cells. We propose a simple kinetic model of transcription initiation and elongation from which we calculate nascent RNA copy-number fluctuations. By testing this theory against published nascent RNA data, we gain new mechanistic insights. Our analytical framework can be used to extract quantitative information about dynamics of transcription from single-cell sequencing data, as well as from single-molecule imaging and electron micrographs of fixed cells, and provides the mathematical means to exploit the quantitative power of these technologies.

Fri 19 Oct, 8:30 - 9:15, Aula Dini
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