Signalling in space and time: systems dynamics of intracellular communication.
Ontology highlight
ABSTRACT:
SUBMITTER: Tzlil S
PROVIDER: S-EPMC3166472 | biostudies-other | 2011 Sep
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Temporal dynamics are coupled to spatial gradients of signalling activities, which guide pivotal intracellular processes and tightly regulate signal propagation across a cell. Computational models provide insights into the complex relationships between the stimuli and the cellular responses, and reveal the mechanisms that are responsible for signal amplification, noise reduction and generation of discontinuous bistable dynamics or oscillations.
| S-EPMC1679905 | biostudies-literature
Project description:Although we have amassed extensive catalogues of signalling network components, our understanding of the spatiotemporal control of emergent network structures has lagged behind. Dynamic behaviour is starting to be explored throughout the genome, but analysis of spatial behaviours is still confined to individual proteins. The challenge is to reveal how cells integrate temporal and spatial information to determine specific biological functions. Key findings are the discovery of molecular signalling machines such as Ras nanoclusters, spatial activity gradients and flexible network circuitries that involve transcriptional feedback. They reveal design principles of spatiotemporal organization that are crucial for network function and cell fate decisions.
| S-EPMC2977972 | biostudies-literature
Project description:The immune system is essential for maintaining homeostasis, as well as promoting growth and healing throughout the brain and body. Considering that immune cells respond rapidly to changes in their microenvironment, they are very difficult to study without affecting their structure and function. The advancement of non-invasive imaging methods greatly contributed to elucidating the physiological roles performed by immune cells in the brain across stages of the lifespan and contexts of health and disease. For instance, techniques like two-photon in vivo microscopy were pivotal for studying microglial functional dynamics in the healthy brain. Through these observations, their interactions with neurons, astrocytes, blood vessels and synapses were uncovered. High-resolution electron microscopy with immunostaining and 3D-reconstruction, as well as super-resolution fluorescence microscopy, provided complementary insights by revealing microglial interventions at synapses (phagocytosis, trogocytosis, synaptic stripping, etc.). In addition, serial block-face scanning electron microscopy has provided the first 3D reconstruction of a microglial cell at nanoscale resolution. This review will discuss the technical toolbox that currently allows to study microglia and other immune cells in the brain, as well as introduce emerging methods that were developed and could be used to increase the spatial and temporal resolution of neuroimmune imaging. A special attention will also be placed on positron emission tomography and the development of selective functional radiotracers for microglia and peripheral macrophages, considering their strong potential for research translation between animals and humans, notably when paired with other imaging modalities such as magnetic resonance imaging.
| S-EPMC7539119 | biostudies-literature
Project description:How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.
| S-EPMC5895055 | biostudies-literature
Project description:Underdominance systems can quickly spread through a population, but only when introduced in considerable numbers. This promises a gene drive mechanism that is less invasive than homing drives, potentially enabling new approaches in the fight against vector-borne diseases. If regional confinement can indeed be achieved, the decision-making process for a release would likely be much simpler compared to other, more invasive types of drives. The capacity of underdominance gene drive systems to spread in a target population without invading other populations is typically assessed via network models of panmictic demes linked by migration. However, it remains less clear how such systems would behave in more realistic population models where organisms move over a continuous landscape. Here, we use individual-based simulations to study the dynamics of several proposed underdominance systems in continuous-space. We find that all these systems can fail to persist in such environments, even after an initially successful establishment in the release area, confirming previous theoretical results from diffusion theory. At the same time, we find that a two-locus two-toxin-antidote system can invade connected demes through a narrow migration corridor. This suggests that the parameter space where underdominance systems can establish and persist in a release area while at the same time remaining confined to that area could be quite limited, depending on how a population is spatially structured. Overall, these results indicate that realistic spatial context must be considered when assessing strategies for the deployment of underdominance drives.
| S-EPMC8284921 | biostudies-literature
Project description:Luminescent solar concentrators (LSCs) have recently emerged as a promising receiver technology in free-space optical communications due to their inherent ability to collect light from a wide field-of-view and concentrate it into small areas, thus leading to high optical gains. Several high-speed communication systems integrating LSCs in their detector blocks have already been demonstrated, with the majority of efforts so far being devoted to maximising the received optical power and the system's field-of-view. However, LSCs may pose a severe bottleneck on the bandwidth of such communication channels due to the comparably slow timescale of the fluorescence events involved, a situation further aggravated by the inherent reabsorption in these systems, and yet, an in-depth study into such dynamic effects remains absent in the field. To fill this gap, we have developed a comprehensive analytical solution that delineates the fundamental bandwidth limits of LSCs as optical detectors in arbitrary free-space optical links, and establishes their equivalence with simple RC low-pass electrical circuits. Furthermore, we demonstrate a time-domain Monte Carlo simulation platform, an indispensable tool in the multiparameter optimisation of LSC-based receiver systems. Our work offers vital insight into LSC system dynamic behaviour and paves the way to evaluate the technology for a wide range of applications, including visible light communications, high-speed video recording, and real-time biological imaging, to name a few.
| S-EPMC7775919 | biostudies-literature
Project description:Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype-phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype-phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy.
| S-EPMC6680062 | biostudies-literature
Project description:The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies.
| S-EPMC4999832 | biostudies-other
Project description:Using the phase-space formulation of quantum mechanics, we derive a four-component Wigner equation for a system composed of spin-[Formula: see text] fermions (typically, electrons) including the Zeeman effect and the spin-orbit coupling. This Wigner equation is coupled to the appropriate Maxwell equations to form a self-consistent mean-field model. A set of semiclassical Vlasov equations with spin effects is obtained by expanding the full quantum model to first order in the Planck constant. The corresponding hydrodynamic equations are derived by taking velocity moments of the phase-space distribution function. A simple closure relation is proposed to obtain a closed set of hydrodynamic equations.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.
| S-EPMC5360899 | biostudies-literature
Project description:In recent years control theory has been applied to biological systems with the aim of identifying the minimum set of molecular interactions that can drive the network to a required state. However, in an intra-cellular network it is unclear how control can be achieved in practice. To address this limitation we use viral infection, specifically human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV), as a paradigm to model control of an infected cell. Using a large human signalling network comprised of over 6000 human proteins and more than 34000 directed interactions, we compared two states: normal/uninfected and infected. Our network controllability analysis demonstrates how a virus efficiently brings the dynamically organised host system into its control by mostly targeting existing critical control nodes, requiring fewer nodes than in the uninfected network. The lower number of control nodes is presumably to optimise exploitation of specific sub-systems needed for virus replication and/or involved in the host response to infection. Viral infection of the human system also permits discrimination between available network-control models, which demonstrates that the minimum dominating set (MDS) method better accounts for how the biological information and signals are organised during infection by identifying most viral proteins as critical driver nodes compared to the maximum matching (MM) method. Furthermore, the host driver nodes identified by MDS are distributed throughout the pathways enabling effective control of the cell via the high 'control centrality' of the viral and targeted host nodes. Our results demonstrate that control theory gives a more complete and dynamic understanding of virus exploitation of the host system when compared with previous analyses limited to static single-state networks.
| S-EPMC6375943 | biostudies-literature