Mathematical modelling plant signalling networks

During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting

Bioengineering models of cell signaling

Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions

Taxis Equations for Amoeboid Cells

The classical macroscopic chemotaxis equations have previously been derived from an individual-based description of the tactic response of cells that use a "run-and-tumble" strategy in response to environmental cues. Here we derive macroscopic equations for the more complex type of behavioral response characteristic of crawling cells, which detect a signal, extract directional information from a scalar concentration field, and change their motile behavior accordingly. We present several models of increasing complexity for which the derivation of population-level equations is possible, and we show how experimentally-measured statistics can be obtained from the transport equation formalism. We also show that amoeboid cells that do not adapt to constant signals can still aggregate in steady gradients, but not in response to periodic waves. This is in contrast to the case of cells that use a "run-and-tumble" strategy, where adaptation is essential.Comment: 35 pages, submitted to the Journal of Mathematical Biolog

Comparative metagenomic analysis reveals mechanisms for stress response in hypoliths from extreme hyperarid deserts

Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the twometagenomeswere identified. The Antarctic hypolithicmetagenome displayed a high number of sequences assigned to sigma factors, replication,recombination andrepair, translation, ribosomal structure,andbiogenesis. In contrast, theNamibDesert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significantdivergence inthe geneticdeterminantsof aminoacidandnucleotidemetabolismbetween these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes.Fil: Le, Phuong Thi. University of Pretoria; Sudáfrica. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; BélgicaFil: Makhalanyane, Thulani P.. University of Pretoria; SudáfricaFil: Guerrero, Leandro Demián. University of Pretoria; Sudáfrica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vikram, Surendra. University of Pretoria; SudáfricaFil: Van De Peer, Yves. University of Pretoria; Sudáfrica. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; BélgicaFil: Cowan, Don A.. University of Pretoria; Sudáfric

A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues

Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness

Structural and organisational conditions for the appearance of a functionally integrated organisation in the transition from prokaryotic to eukaryotic cell

211 p.The concept of functional (or physiological) integration is explanatorily relevant to both biology andphilosophy of biology, but it suffers from two main related problems: first, it is an umbrella termencompassing any causal interdependence of functions, thus being unsuitable for characterisingbiological organisations as physiologic units; secondly, it lacks a unified theoretical framework tounderstand this concept. This PhD thesis aims to investigate the relationship between functionalintegration and biological individuality by studying the nature and the role of physiological integration inone of the major evolutionary transitions: the origin of the eukaryotic cell from the prokaryotic one. Themethodology employed is the so-called ¿organizational approach¿ that combines the descriptive approachof the methodological naturalism with the normative evaluation of the epistemic and practicalconsequences of the theoretical frameworks of life sciences. At the core of this work is the examinationof the physic-chemical and structural-functional conditions that allowed the transformation of aprokaryote into a eukaryotic cell and that determined a very specific kind of functionally integratedorganisation in eukaryotes. The thesis puts forward a theoretical proposal for functional integrationconsisting in the global capacity, enabled by specific spatial constraints, of a biological organisation toperform system-level regulation, spatio-temporal coordination of the parts, and system-levelreproduction. This proposal for functional integration has important consequences for understandingimportant issues of theoretical biology and philosophy of biology, such as biological individuality,biological autonomy, and major transitions in evolution

Structural and organisational conditions for the appearance of a functionally integrated organisation in the transition from prokaryotic to eukaryotic cell

211 p.The concept of functional (or physiological) integration is explanatorily relevant to both biology andphilosophy of biology, but it suffers from two main related problems: first, it is an umbrella termencompassing any causal interdependence of functions, thus being unsuitable for characterisingbiological organisations as physiologic units; secondly, it lacks a unified theoretical framework tounderstand this concept. This PhD thesis aims to investigate the relationship between functionalintegration and biological individuality by studying the nature and the role of physiological integration inone of the major evolutionary transitions: the origin of the eukaryotic cell from the prokaryotic one. Themethodology employed is the so-called ¿organizational approach¿ that combines the descriptive approachof the methodological naturalism with the normative evaluation of the epistemic and practicalconsequences of the theoretical frameworks of life sciences. At the core of this work is the examinationof the physic-chemical and structural-functional conditions that allowed the transformation of aprokaryote into a eukaryotic cell and that determined a very specific kind of functionally integratedorganisation in eukaryotes. The thesis puts forward a theoretical proposal for functional integrationconsisting in the global capacity, enabled by specific spatial constraints, of a biological organisation toperform system-level regulation, spatio-temporal coordination of the parts, and system-levelreproduction. This proposal for functional integration has important consequences for understandingimportant issues of theoretical biology and philosophy of biology, such as biological individuality,biological autonomy, and major transitions in evolution

Whence Directionality: Guidance Mechanisms in Solitary and Collective Cell Migration

As individual cells or groups of cells move through the complex environment of the body, their migration is affected by multiple external cues. Some cues are diffusible signaling molecules, and some are solid biophysical features. How do cells respond appropriately? This perspective discusses the relationship between guidance input and the cellular output, considering effects from classical chemotaxis to contact-dependent guidance. The influences of membrane trafficking and of imposed constraints on directional movement are also considered. New insights regarding guidance and dynamic cell polarity have emerged from examining new cell migration models and from re-examining well known ones with new approaches and new tools

Cryptochrome photoreceptors in the green alga Chlamydomonas reinhardtii: versatility of functions and mechanisms

Photosynthetic microorganisms, including microalgae and cyanobacteria, account to half of global CO2 fixation. Light governs their photosynthesis and other biological functions. Specifically, cryptochromes, photoreceptors found universally, primarily detect UV-A/blue light and are known to repair DNA. This study focuses on five algal cryptochromes, especially CRY-DASH1 (Drosophila, Arabidopsis, Synechocystis, Homo) in the green alga, Chlamydomonas reinhardtii. Located in the chloroplast, CRY-DASH1's expression peaks around midday. A mutant lacking CRY-DASH1 showed decreased growth but enhanced photosynthesis efficiency. Furthermore, the mutant revealed increased pigment amounts, hyper-stacking of the thylakoid membrane and elevated levels of photosystem II proteins like D1 and CP43, but not of their transcripts. These data suggest that CRY-DASH1 plays its role as regulator at the posttranscriptional/translational level. CRY-DASH1 has an absorption peak in the UV-A range and supplementation of white light with UV-A increases photoautotrophic growth of wild type but not of the mutant lacking CRY-DASH1. Comparative analysis of the chloroplast proteome of wild type and of the mutant revealed that multiple proteins, including key enzymes for the synthesis of chlorophylls and carotenoids, as well as acyl-lipid metabolism and photoprotection, are upregulated in the mutant. In contrast, we found that essential proteins from the central carbon metabolism, are downregulated. Additionally, we discovered that the mutant revealed a downregulation of certain enzymes involved in histidine metabolism which leads to a reduction in the quantity of free histidine. Another cryptochrome, CRY-DASH2, when mutated, exhibited similar growth reduction and pigment increase. The study ends pondering if CRY-DASH1 and CRY-DASH2 might have overlapping functionalities