A Deterministic Model for One-Dimensional Excluded Flow with Local Interactions

Natural phenomena frequently involve a very large number of interacting molecules moving in confined regions of space. Cellular transport by motor proteins is an example of such collective behavior. We derive a deterministic compartmental model for the unidirectional flow of particles along a one-dimensional lattice of sites with nearest-neighbor interactions between the particles. The flow between consecutive sites is governed by a soft simple exclusion principle and by attracting or repelling forces between neighboring particles. Using tools from contraction theory, we prove that the model admits a unique steady-state and that every trajectory converges to this steady-state. Analysis and simulations of the effect of the attracting and repelling forces on this steady-state highlight the crucial role that these forces may play in increasing the steady-state flow, and reveal that this increase stems from the alleviation of traffic jams along the lattice. Our theoretical analysis clarifies microscopic aspects of complex multi-particle dynamic processes

Early Replicons: Origin and Evolution

RNA and protein molecules were found to be both templates for replication and specific catalysts for biochemical reactions. RNA molecules, although very difficult to obtain via plausible synthetic pathways under prebiotic conditions, are the only candidates for early replicons. Only they are obligatory templates for replication, which can conserve mutations and propagate them to forthcoming generations. RNA based catalysts, called ribozymes, act with high efficiency and specificity for all classes of reactions involved in the interconversion of RNA molecules such as cleavage and template assisted ligation. The idea of an RNA world was conceived for a plausible prebiotic scenario of RNA molecules operating upon each other and constituting thereby a functional molecular organization. A theoretical account on molecular replication making precise the conditions under which one observes parabolic, exponential or hyperbolic growth is presented. Exponential growth is observed in a protein assisted RNA world where plus-minus-(±)-duplex formation is avoided by the action of an RNA replicase. Error propagation to forthcoming generations is analyzed in absence of selective neutral mutants as well as for predefined degrees of neutrality. The concept of an error threshold for sufficiently precise replication and survival of populations derived from the theory of molecular quasispecies is discussed. Computer simulations are used to model the interplay between adaptive evolution and random drift. A model of evolution is proposed that allows for explicit handling of phenotypes

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. It is a challenge to understand how this transport is organized, given that it takes place in a confined environment and that several types of motors moving in opposite directions are involved. We review several features that could contribute to the efficiency of this transport, including the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we discuss some still open questions.Comment: 74 pages, 43 figure

Recognizing and engineering digital-like logic gates and switches in gene regulatory networks

A central aim of synthetic biology is to build organisms that can perform useful activities in response to specified conditions. The digital computing paradigm which has proved so successful in electrical engineering is being mapped to synthetic biological systems to allow them to make such decisions. However, stochastic molecular processes have graded input-output functions, thus, bioengineers must select those with desirable characteristics and refine their transfer functions to build logic gates with digital-like switching behaviour. Recent efforts in genome mining and the development of programmable RNA-based switches, especially CRISPRi, have greatly increased the number of parts available to synthetic biologists. Improvements to the digital characteristics of these parts are required to enable robust predictable design of deeply layered logic circuits

Isolierung und Charakterisierung von Myxobakterien und anderen seltenen Meeresbakterien und deren Multilocus-Sequenzanalyse der indonesischen Biodiversität

Indonesia is a country with high potential in biodiversity exploration, especially for microorganisms. This study used samples collected from the islands of Java, Sulawesi, and Bali under the Germany-Indonesia Antiinfectives Cooperation (GINAICO) project. We have isolated 59 strains of gliding bacteria, 98% of which are myxobacteria while the remaining 2% is made up of other gliding bacteria. In this research, we have identified a rare myxobacterium and a novel non-myxobacterial strain from our selected samples. Finally, we confirmed the effectiveness of housekeeping genes as a core method in analysing the degree of relatedness between different strains. The strain Soce1964KM was found to be closest to the rare genus Sorangium and strain 1932KM was identified as a novel genus in the family Flammeovirgaceae. Both results are according to the analysis of its 16S rRNA gene sequence and whole-genome sequencing analysis for strain 1932KM. We also performed screening for antiinfectives against Escherichia coli, Candida albicans and Staphylococcus aureus. Strain Soce1964KM has the highest activity against Staphylococcus aureus and Candida albicans. Analysis of the methanol extract of Soce1964KM through the chromatogram from High-Pressure Liquid Chromatography (HPLC) and High-Resolution Electrospray Ionisation Mass Spectrometry (HRESIMS)–in addition to the database in Myxobase–showed that the extract contains a known compound, namely Disorazol. We found 1932KM to be a novel strain after an in-depth examination of this strain’s phenotype and genotype as part of a polyphasic taxonomy analysis. Also, we conducted a gene cluster analysis and bioassay against pathogenic bacteria and statistical analysis of 16S rRNA gene sequences from this strain with the statistical tool PAST. Bioinformatic tools, such as Prokka, RAST, AntiSmash, NP.searcher, PubChem, SMART and Molinspiration, were used for an in-depth analysis of the whole-genome sequence. Strain 1932KM has also obtained a deposition number from the Indonesian Culture Collections, namely InaCC B1242 with the proposed name of Balibacter flavus gen.nov.sp.nov. Meanwhile, we used the housekeeping genes pgm, pyrG and rpoB to analyse the relatedness between the genera Corallococcus and Myxococcus. These housekeeping genes were used in this study as the core to analyse the similarities between the isolated strains and the type strains. The analysis involved the reconstruction of a phylogenetic tree and its polymorphisms. Bioinformatics tools supported these analyses. These analyses showed that the method is suitable for preliminary analysis in the search for novel species and/or subspecies.Indonesien ist ein Land mit hohem Potenzial für die Erforschung der biologischen Vielfalt, insbesondere für Mikroorganismen. In dieser Studie wurden Proben verwendet, die auf den Inseln Java, Sulawesi, und Bali im Rahmen des Projekts GINAICO (Deutschland-Indonesien Antiinfectives Cooperation) gesammelt wurden. Wir haben 59 Stämme gleitender Bakterien isoliert, von denen 98% Myxobakterien sind, während die restlichen 2% aus anderen gleitenden Bakterien bestehen. In dieser Studie haben wir aus unseren ausgewählten Proben ein seltenes Myxobakterium und einen neuartigen nicht-myxobakteriellen Stamm identifiziert. Schließlich bestätigten wir die Wirksamkeit von Housekeeping-Genen als Kernmethode bei der Analyse des Grads der Verwandtschaft zwischen verschiedenen Stämmen. Es wurde festgestellt, dass der Stamm Soce1964KM der seltenen Gattung Sorangium am nächsten kommt, und der Stamm 1932KM wurde als neuartige Gattung in der Familie der Flammeovirgaceae identifiziert. Beide Ergebnisse entsprechen der Analyse seiner 16S-rRNA-Gensequenz und der Gesamtgenomsequenzierungsanalyse für den Stamm 1932KM. Wir führten auch ein Screening auf Antiinfektiva gegen Escherichia coli, Candida albicans und Staphylococcus aureus durch. Der Stamm Soce1964KM hat die höchste Aktivität gegen Staphylococcus aureus und Candida albicans. Die Analyse des Methanolextrakts von Soce1964KM mittels Chromatogramms aus Hochdruckflüssigchromatographie (HPLC) und hochauflösender Elektrospray-Ionisationsmassenspektrometrie (HRESIMS) - zusätzlich zur Datenbank in Myxobase - zeigte, dass der Extrakt eine bekannte Verbindung enthält, nämlich Disorazol. Nach einer eingehenden Untersuchung des Phänotyps und Genotyps dieses Stammes im Rahmen einer mehrphasigen Taxonomieanalyse stellten wir fest, dass 1932KM ein neuartiger Stamm ist. Außerdem führten wir mit dem statistischen Tool PAST eine Genclusteranalyse und einen Bioassay gegen pathogene Bakterien sowie eine statistische Analyse der 16S-rRNA-Gensequenzen dieses Stammes durch. Bioinformatische Werkzeuge wie Prokka, RAST, AntiSmash, NP.searcher, PubChem, SMART und Molinspiration wurden für eine eingehende Analyse der gesamten Genomsequenz verwendet. Der Stamm 1932KM hat auch eine Hinterlegungsnummer aus den indonesischen Kultursammlungen erhalten, nämlich InaCC B1242 mit dem vorgeschlagenen Namen Balibacter flavus gen.nov.sp.nov. In der Zwischenzeit haben wir die Housekeeping-Gene pgm, pyrG und rpoB verwendet, um die Verwandtschaft zwischen den Gattungen Corallococcus und Myxococcus zu analysieren. Diese Housekeeping-Gene wurden in dieser Studie als Kern verwendet, um die Ähnlichkeiten zwischen den isolierten Stämmen und den Typstämmen zu analysieren. Die Analyse umfasste die Rekonstruktion eines phylogenetischen Baums und seiner Polymorphismen. Bioinformatik-Tools unterstützten diese Analysen. Diese Untersuchungen zeigten, dass die Methode für eine vorläufige Analyse bei der Suche nach neuen Arten und / oder Unterarten geeignet ist