Benedikt von Bronk | Searcharxiv

arXiv2019

Boosting Functional Response Models for Location, Scale and Shape with an Application to Bacterial Competition

We extend Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to regression with functional response. This allows us to simultaneously model point-wise mean curves, variances and other distributional parameters of the response in dependence of various scalar and functional covariate effects. In addition, the scope of distributions is extended beyond exponential families. The model is fitted via gradient boosting, which offers inherent model selection and is shown to be suitable for both complex model structures and highly auto-correlated response curves. This enables us to analyze bacterial growth in \textit{Escherichia coli} in a complex interaction scenario, fruitfully extending usual growth models.

stat.ME↗

arXiv2018

CsrA and its regulators control the time-point of ColicinE2 release in Escherichia coli

The bacterial SOS response is a cellular reaction to DNA damage, that, among other actions, triggers the expression of colicin - toxic bacteriocins in Escherichia coli that are released to kill close relatives competing for resources. However, it is largely unknown, how the complex network regulating toxin expression controls the time-point of toxin release to prevent premature release of inefficient protein concentrations. Here, we study how different regulatory mechanisms affect production and release of the bacteriocin ColicinE2 in Escherichia coli. Combining experimental and theoretical approaches, we demonstrate that the global carbon storage regulator CsrA controls the duration of the delay between toxin production and release and emphasize the importance of CsrA sequestering elements for the timing of ColicinE2 release. In particular, we show that ssDNA originating from rolling-circle replication of the toxin-producing plasmid represents a yet unknown additional CsrA sequestering element, which is essential in the ColicinE2-producing strain to enable toxin release by reducing the amount of free CsrA molecules in the bacterial cell. Taken together, our findings show that CsrA times ColicinE2 release and reveal a dual function for CsrA as an ssDNA and mRNA-binding protein, introducing ssDNA as an important post-transcriptional gene regulatory element.

q-bio.MN↗