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Silvia Grigolon

Publications and source records attributed to Silvia Grigolon.

7 recordsLinked to original sources

Disordered Yet Directed: The Emergence of Polar Flocks with Disordered Interactions

Flocking is a prime example of how robust collective behavior can emerge from simple interaction rules. The flocking transition has been studied extensively since the inception of the original Vicsek model. Here, we introduce a self-propelled particle model with quenched disorder in the pairwise alignment interaction couplings akin to a spin-glass model. We find that increasing the variance of the coupling distribution can promote (rather than destroy) the emergence of global polar order. In particular, we show that our model can display a flocking phase even when the majority of the interaction couplings are antialigning. Activity is the key ingredient to reduce frustration in the system as it allows local particle clustering combined with self-organization of the particles to favor neighborhoods with strong cooperative interactions.

cond-mat.soft

microRNA-mediated noise processing in cells: a fight or a game?

In the past decades microRNAs (miRNA) have much attracted the attention of researchers at the interface between life and theoretical sciences for their involvement in post-transcriptional regulation and related diseases. Thanks to the always more sophisticated experimental techniques, the role of miRNAs as "noise processing units" has been further elucidated and two main ways of miRNA noise-control have emerged by combinations of theoretical and experimental studies. While on one side miRNA were thought to buffer gene expression noise, it has recently been suggested that miRNA could also increase the cell-to-cell variability of their targets. In this Mini Review, we focus on the miRNA role in noise processing and on the inference of the parameters defined by the related theoretical modelling.

q-bio.MN

Plant responses to auxin signals: an operating principle for dynamical sensitivity yet high resilience

Plants depend on the signaling of the phytohormone auxin for their development and for responding to environmental perturbations. The associated biomolecular signaling network involves a negative feedback at the level of the Aux/IAA proteins which mediate the influence of auxin (the signal) on the ARF transcription factors (the drivers of the response). To probe the role of this feedback, we consider alternative in silico signaling networks implementing different operating principles. By a comparative analysis, we find that the presence of a negative regulatory feedback loop allows the system to have a far larger sensitivity in its dynamical response to auxin. At the same time, this sensitivity does not prevent the system from being highly resilient. Given this insight, we reconsider previously published models and build a new quantitative and calibrated biomolecular model of auxin signaling.

q-bio.MN

On the role of extrinsic noise in microRNA-mediated bimodal gene expression

Several studies highlighted the relevance of extrinsic noise in shaping cell decision making and differentiation in molecular networks. Experimental evidences of phenotypic differentiation are given by the presence of bimodal distributions of gene expression levels, where the modes of the distribution often correspond to different physiological states of the system. We theoretically address the presence of bimodal phenotypes in the context of microRNA (miRNA)-mediated regulation. MiRNAs are small noncoding RNA molecules that downregulate the expression of their target mRNAs. The nature of this interaction is titrative and induces a threshold effect: below a given target transcription rate no mRNAs are free and available for translation. We investigate the effect of extrinsic noise on the system by introducing a fluctuating miRNA-transcription rate. We find that the presence of extrinsic noise favours the presence of bimodal target distributions which can be observed for a wider range of parameters compared to the case with intrinsic noise only and for lower miRNA-target interaction strength. Our results suggest that combining threshold-inducing interactions with extrinsic noise provides a simple and robust mechanism for obtaining bimodal populations not requiring fine tuning. We furthermore characterise the protein distributions dependence on protein half-life.

q-bio.MN

Noise Processing by MicroRNA-Mediated Circuits: the Incoherent Feed-Forward Loop, Revisited

The intrinsic stochasticity of gene expression is usually mitigated in higher eukaryotes by post-transcriptional regulation channels that stabilise the output layer, most notably protein levels. The discovery of small non-coding RNAs (miRNAs) in specific motifs of the genetic regulatory network has led to identifying noise buffering as the possible key function they exert in regulation. Recent in vitro} and in silico studies have corroborated this hypothesis. It is however also known that miRNA-mediated noise reduction is hampered by transcriptional bursting in simple topologies. Here, using stochastic simulations validated by analytical calculations based on van Kampen's expansion, we revisit the noise-buffering capacity of the miRNA-mediated Incoherent Feed Forward Loop (IFFL), a small module that is widespread in the gene regulatory networks of higher eukaryotes, in order to account for the effects of intermittency in the transcriptional activity of the modulator gene. We show that bursting considerably alters the circuit's ability to control static protein noise. By comparing with other regulatory architectures, we find that direct transcriptional regulation significantly outperforms the IFFL in a broad range of kinetic parameters. This suggests that, under pulsatile inputs, static noise reduction may be less important than dynamical aspects of noise and information processing in characterising the performance of regulatory elements.

q-bio.MN

Identifying relevant positions in proteins by Critical Variable Selection

Evolution in its course found a variety of solutions to the same optimisation problem. The advent of high-throughput genomic sequencing has made available extensive data from which, in principle, one can infer the underlying structure on which biological functions rely. In this paper, we present a new method aimed at extracting sites encoding structural and func- tional properties from a set of protein primary sequences, namely a Multiple Sequence Alignment. The method, called Critical Variable Selection, is based on the idea that subsets of relevant sites cor- respond to subsequences that occur with a particularly broad frequency distribution in the dataset. By applying this algorithm to in silico sequences, to the Response Regulator Receiver and to the Voltage Sensor Domain of Ion Channels, we show that this procedure recovers not only information encoded in single site statistics and pairwise correlations but it also captures dependencies going beyond pairwise correlations. The method proposed here is complementary to Statistical Coupling Analysis, in that the most relevant sites predicted by the two methods markedly differ. We find robust and consistent results for datasets as small as few hundred sequences, that reveal a hidden hierarchy of sites that is consistent with present knowledge on biologically relevant sites and evo- lutionary dynamics. This suggests that Critical Variable Selection is able to identify in a Multiple Sequence Alignment a core of sites encoding functional and structural information.

q-bio.QM

Modeling the emergence of polarity patterns for the intercellular transport of auxin in plants

The hormone auxin is actively transported throughout plants via protein machineries including the dedicated transporter known as PIN. The associated transport is ordered with nearby cells driving auxin flux in similar directions. Here we provide a model of both the auxin transport and of the dynamics of cellular polarisation based on flux sensing. Our main findings are: (i) spontaneous intracellular PIN polarisation arises if PIN recycling dynamics are sufficiently non-linear, (ii) there is no need for an auxin concentration gradient, and (iii) ordered multi-cellular patterns of PIN polarisation are favored by molecular noise.

q-bio.TO