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Priya Chakraborty

Publications and source records attributed to Priya Chakraborty.

9 recordsLinked to original sources

Bistability to Quad-stability: Emergence of Hybrid Phenotypes & Enhanced Spatio-temporal Plasticity in Presence of Host-Circuit Coupling

In the context of multistability driven diseases, like cancer, spatiotemporal plasticity plays a significant role to achieve a spectrum of phenotypic variations. The interplay between gene regulatory networks and environmental factors, such as resource competition and spatial diffusion, plays a crucial role in determining cellular behaviour and phenotypic heterogeneity. Though reaction diffusion frameworks have been widely applied in developmental biology, less attention has been paid to the simultaneous effects of resource competition and growth feedback on spatial organization. In this paper, we observed that a bistable genetic circuit under high resource competition due to growth feedback gives rise to multiple emergent phenotypes, as observed in cancer systems. Furthermore, we observed how spatial diffusion coupled with intrinsic nonlinearity can drive the emergence of distinct spatial dynamics over time. The observed spatiotemporal plasticity can also be driven by the comparative stability of the fixed points, diffusivity, and asymmetry of diffusion. Our findings highlight that growth-induced resource competition combined with diffusion can provide deeper insights into metastasis and cancer progression.

q-bio.PE

Sustainability & Social Segmentation in Social Media Contagion: A Mathematical and Computational Study on Dual Effects of Individual Needs & Peer Influence

Addiction to internet-based social media has increasingly emerged as a critical social problem, especially among young adults and teenagers. Based on multiple research studies, excessive usage of social media may have detrimental psychological and physical impacts. In this study, we are going to explore mathematically the dynamics of social media addiction behaviour and explore the determinants of compulsive use of social media from the dual perspectives of individual needs or cravings and peer-related factors or peer pressure. The theoretical analysis of the model without the peer pressure effect reveals that the associated addiction-free equilibrium is globally stable whenever a certain threshold, known as the addictive-generation number, is less than unity and unstable when the threshold is greater than unity. We observed how introduction of peer influence adds a sustainability to the dynamics, and causes a multistability, through which addiction-contagion can proliferate, even below the designated critical threshold. Using simulations over model networks, we demonstrate our finding, even in the presence of social heterogeneity. Finally, we use the reaction-diffusion approach to investigate spatio-temporal dynamics in a synthetic society, in the form of a 2D lattice. Instead of a fast convergence to the steady states, we observe a long transient of social clustering and segmentation, represented by spatio-temporal pattern formation. Our model illustrates how the peer influence factor plays a crucial role and concludes that it is required to consider the peer factors while formulating specific strategies that could be more effective against this addiction and its potential adverse outcomes.

physics.soc-ph

Resource competition in Three-gene-motif & Emergence of Feed-forward response: A Spatiotemporal Study

Feed-forward dynamics, which is well-known to have several important implications in nonlinear dynamical systems, frequently occurs in gene expression motifs, and has been well explored experimentally and mathematically. However, dependency of the components of a genetic circuit upon its host, due to the requirement for resources like ribosome, ATP, transcription factors, tRNA, etc., and related effects are of utmost importance, which is commonly ignored in mathematical models. In a resource-limited environment, two apparently unconnected genes can compete for resources for their respective expression and may exhibit indirect regulatory connection; an emergent response thus arises in the system completely because of resource competition. In this work, we have shown how the responses of the feed-forward loop (FFL), a well-studied regulatory genetic motif, can be recreated considering the resource competition in a three-gene pathway. Exploring the genetic system with temporal as well as spatiotemporal stability analysis, interesting transient and steady-state responses have been observed. The genetic motifs explored in this paper show many of the characteristic features of the conventional FFL structure, like response delay and pulse generation. Most interestingly, in a two-dimensional cellular arrangement, characteristic pattern formation under a concentration gradient of input signals have also been observed. This study pinpoints a larger area of research and exploration in synthetic and cellular systems, which will reveal novel controlling ideas and unique behavioral changes in the system for its context dependencies.

q-bio.MN

Visual Representation for Patterned Proliferation of Social Media Addiction: Quantitative Model and Network Analysis

With the advancement of information technology, more people, especially young adults, are getting addicted to the use of different social media platforms. Despite immense useful applications in communication and interactions, the habit of spending excessive time on these social media platforms is becoming addictive, causing different consequences, like anxiety, depression, health problems, and many more. Here, we mathematically explored a model of social media addiction, including a peer-influence relapse. We have further done the complex network analysis for a heterogenic synthetic society. Finally, we explore spatiotemporal pattern formation in a diffusive social system using the reaction-diffusion approach. Our model shows how the existent nonlinearity in the system makes it difficult to make society social media addiction free once it crosses a certain threshold. Some possible strategies are explored mathematically to prevent social media addiction, and the importance of peer-influenced relapse has been identified as a major barrier.

physics.soc-ph

Quantitative Modelling of Diffusion-driven Pattern Formation in microRNA-regulated Gene Expression

MicroRNAs are extensively known for post-transcriptional gene regulation and pattern formation in the embryonic developmental stage. We explore the origin of these spatio-temporal patterns mathematically, considering three different motifs here. For three scenarios, (1) simple microRNA-based mRNA regulation with a graded response in output, (2) microRNA-based mRNA regulation resulting in bistability in the dynamics, and (3) a coordinated response of microRNA (miRNA), simultaneously regulating the mRNAs of two different pools, detailed dynamical analysis, as well as the reaction-diffusion scenario have been considered and analyzed in the steady state and for the transient dynamics further. We have observed persistent-temporal patterns, as a result of the dynamics of the motifs, that explain spatial gradients and relevant patterns formed by related proteins in development and phenotypic heterogenetic aspects in biological systems. Competitive effects of miRNA regulation have also been found to be capable to cause spatio-temporal patterns, persistent enough to direct developmental decisions. Under coordinated regulation, miRNAs are found to generate spatio-temporal patterning even from complete homogeneity in concentration of target protein, which may have impactful insights in choice of cell-fates.

q-bio.QM

Spatio-temporal Pattern Formation due to Host-Circuit Interplay in Gene Expression Dynamics

Biological systems are majorly dependent on their property of bistability in order to exhibit nongenetic heterogeneity in terms of cellular morphology and physiology. Spatial patterns of phenotypically heterogeneous cells, arising due to underlying bistability, may play significant role in phenomena like biofilm development, adaptation, cell motility etc. While nonlinear positive feedback regulation, like cooperative heterodimer formation are the usual reason behind bistability, similar dynamics can also occur as a consequence of host-circuit interaction. In this paper, we have investigated the pattern formation by a motif with non-cooperative positive feedback, that imposes a metabolic burden on its host due to its expression. In a cellular array set inside diffusible environment, we investigate spatio-temporal diffusion in one dimension as well as in two dimension in the context of various initial conditions respectively. Moreover, the number of cells exhibiting the same steady state, as well as their spatial distribution has been quantified in terms of connected component analysis. The effect of diffusion coefficient variation has been studied in terms of stability of related states and time evolution of patterns.

q-bio.QM

Resource allocation determines alternate cell fate in Bistable Genetic Switch

Living cells need a constant availability of certain resources to have a sustained gene expression process. Limited availability of cellular resources for gene expression, like ribosomes, along with a variation of resource affinity, significantly modifies the system dynamics. Factors like the variation in rate of binding, or variation in efficiency of the recruited resource have the potential to affect crucial dynamical phenomena like cell fate determination. In this paper, we have taken a very important motif, a bistable genetic toggle switch, and explored the effect of resource imbalance in this circuit in terms of the bifurcations taking place. We show that initial asymmetric biasing to resource via resource affinity or gene copy number, significantly modifies the cell fate transition, both in pitchfork and saddle node type bifurcation. Our study establishes that in a limited resource environment, controlled resource allocation can be an important factor for robust functioning of the synthetic or cellular genetic switches.

q-bio.QM

Emergent Regulatory Response and Shift of Half induction point under Resource Competition in Genetic circuits

Synthetic genetic circuits are implemented in living cells for their operation. During gene expression, proteins are produced from the respective genes, by formation of complexes through the process of transcription and translation. In transcription the circuit uses RNAP, etc. as resource from the host cell and in translation, ribosome, tRNA and other cellular resources are supplied to the operating circuit. As the cell contains these resources in limited number, the circuit can suffer from unprecedented resource competition which might destroy the circuit functionality, or introduce some emergent responses. In this paper, we have studied a three-gene motif under resource competition where interesting behaviour, similar to regulatory responses occur due to limited supply of necessary resources. The system of interest exhibits prominent changes in behaviour which can be observed experimentally. We focus on two specific aspects, namely, dynamic range and half-induction point, which inherently describe the circuit functionalities, and can be affected by corresponding resource affinity and availability.

q-bio.MN

Emergent Correlations in Gene Expression Dynamics as Footprints of Resource Competition

Genetic circuits need a cellular environment to operate in, which naturally couples the circuit function with the overall functionality of gene regulatory network. To execute their functions all gene circuits draw resources in the form of RNA polymerases, ribosomes, and tRNAs. Recent experiments pointed out that the role of resource competition on synthetic circuit outputs could be immense. However, the effect of complexity of the circuit architecture on resource sharing dynamics is yet unexplored. In this paper, we employ mathematical modelling and in-silico experiments to identify the sources of resource trade-off and to quantify its impact on the function of a genetic circuit, keeping our focus on regulation of immediate downstream proteins. We take the example of the fluorescent reporters, which are often used as protein read-outs. We show that estimating gene expression dynamics from readings of downstream protein data might be unreliable when the resource is limited and ribosome affinities are asymmetric. We focus on the impact of mRNA copy number and RBS strength on the nonlinear isocline that emerges with two regimes, prominently separated by a tipping point, and study how correlation and competition dominate each other depending on various circuit parameters. Focusing further on genetic toggle circuit, we have identified major effects of resource competition in this model motif, and quantified the observations. The observations are testable in wet-lab experiments, as all the parameters chosen are experimentally relevant.

q-bio.QM