End-of-year Biomath Symposium

Abstract:

Live-cell imaging experiments often track mRNA production using fluorescently tagged transcripts. To infer the statistics of initiation events, standard methods assume that transcription has a fixed duration. However, studies of intron splicing and transcriptional pausing show that stochasticity in elongation and termination are often significant and cannot be ignored. In this talk, we advocate an alternative approach: fitting directly to the autocorrelation function of the fluorescence intensity signal. Building on recent links between transcriptional models and infinite‑server queueing systems, we use theoretical autocorrelation expressions to infer parameters in models that incorporate stochasticity in both gene switching and transcription time. This framework provides richer mechanistic insight than approaches requiring fixed transcription durations. We illustrate its advantages using recent live‑cell imaging data, fitting autocorrelations under a delay Telegraph model that includes an additional exponential waiting time in the transcription process.

14:30-15:00 Coffee Break

Abstract:

Epigenetic modifications of the DNA and chromatin play key roles in development, regeneration and ageing. Experimental breakthroughs in single-cell biology now allow us to profile the epigenome with unprecedented detail. Drawing on these experiments, I will show how methods from statistical physics can unveil the biophysical principles that govern the time evolution of the epigenome. In the first part of my talk, I will discuss the biophysical processes that underly the formation of the embryonic epigenome and make sense of an unexpected observation of self-similar scaling in DNA methylation. Changes in the epigenome are also tighly related to the progression of ageing. In the second part of my talk I will use experiments spanning different temporal scales to show how the time scale of epigenetic ageing derives from the fast molecular processes that maintain the epigenome.