Inferring the directionality of interactions between cellular processes is a major challenge in systems biology. Time-lagged correlations allow to discriminate between alternative models, but they still rely on assumed underlying interactions. Here, we show that an information-theoretic quantity, the transfer entropy (TE), quantifies the directional influence between fluctuating variables in a model-free way. We present a theoretical approach to compute the transfer entropy, even when the noise has an extrinsic component or in the presence of feedback. We re-analyze the experimental data from Kiviet et al. (2014) [1], where fluctuations in gene expression of metabolic enzymes and growth rate have been measured in single cells of Escherichia coli. We confirm the formerly detected modes between growth and gene expression, while prescribing more stringent conditions on the structure of noise sources [2]. [1] Stochasticity of metabolism and growth at the single-cell level, D. J. Kiviet et al., Nature, 514, 376 (2014).[2] Information theoretic…

.

Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of lncRNA which functions on the epigenome remain to be deciphered. Recent works showed that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Here, I will present data providing insights on their regulatory activity which is conserved also in S. pombe containing RNAi pathway. The transcription and post-transcription-mediated regulatory activities of antisense…

Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of lncRNA which functions on the epigenome remain to be deciphered. Recent works showed that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Here, I will present data providing insights on their regulatory activity which is conserved also in S. pombe containing RNAi pathway. The transcription and post-transcription-mediated regulatory activities of antisense…

Mutations have been investigated for more than a century but never witnessed in action in single cells, thus preventing direct characterization of their dynamics and reliable estimation of the distribution of their fitness effects. Such estimates have wide application and are critical for most evolutionary models/studies. We accomplished this in Escherichia coli by employing microfluidics, time-lapse imaging, and by visualizing mutations in single cells by using a fluorescent tag of the Mismatch Repair System. I will present our results obtained for strains having a wide range of mutation rates and growing under controlled condition in the absence of exogenous stress.

The emerging field of compartmentalized in vitro evolution, where selection is carried out by differential reproduction in each compartment, is a promising new approach to protein engineering. From practical point of view, it is important to know the effect of the increase in the average number of genotype bearing agents per compartment. This effect is also interesting on its own in the context of primordial evolution in the hypothetical RNA world. The question is important as genotypes with different phenotypes in the same compartment share their fitness (the number of produced copies) rendering the selection frequency-dependent. I will show the results of a theoretical investigation of this problem in the context of selection dynamics for a simple model with an infinite population that is periodically redistributed among infinite number of identical compartments, inside which all molecules are copied without distinction with the success rate as a function of the total genomic composition…

.