ترغب بنشر مسار تعليمي؟ اضغط هنا

A biologically motivated three-species exclusion model: effects of leaky scanning and overlapping genes on initiation of protein synthesis

73   0   0.0 ( 0 )
 نشر من قبل Debashish Chowdhury
 تاريخ النشر 2018
  مجال البحث فيزياء
والبحث باللغة English




اسأل ChatGPT حول البحث

Totally asymmetric simple exclusion process (TASEP) was originally introduced as a model for the traffic-like collective movement of ribosomes on a messenger RNA (mRNA) that serves as the track for the motor-like forward stepping of individual ribosomes. In each step, a ribosome elongates a protein by a single unit using the track also as a template for protein synthesis. But, pre-fabricated, functionally competent, ribosomes are not available to begin synthesis of protein; a subunit directionally scans the mRNA in search of the pre-designated site where it is supposed to bind with the other subunit and begin the synthesis of the corresponding protein. However, because of `leaky scanning, a fraction of the scanning subunits miss the target site and continue their search beyond the first target. Sometimes such scanners successfully identify the site that marks the site for initiation of the synthesis of a different protein. In this paper, we develop an exclusion model, with three interconvertible species of hard rods, to capture some of the key features of these biological phenomena and study the effects of the interference of the flow of the different species of rods on the same lattice. More specifically, we identify the meantime for the initiation of protein synthesis as appropriate mean {it first-passage} time that we calculate analytically using the formalism of backward master equations. In spite of the approximations made, our analytical predictions are in reasonably good agreement with the numerical data that we obtain by performing Monte Carlo simulations. We also compare our results with a few experimental facts reported in the literature and propose new experiments for testing some of our new quantitative predictions.

قيم البحث

اقرأ أيضاً

We develope a theoretical framework, based on exclusion process, that is motivated by a biological phenomenon called transcript slippage (TS). In this model a discrete lattice represents a DNA strand while each of the particles that hop on it unidire ctionally, from site to site, represents a RNA polymerase (RNAP). While walking like a molecular motor along a DNA track in a step-by-step manner, a RNAP simultaneously synthesizes a RNA chain; in each forward step it elongates the nascent RNA molecule by one unit, using the DNA track also as the template. At some special slippery position on the DNA, which we represent as a defect on the lattice, a RNAP can lose its grip on the nascent RNA and the latters consequent slippage results in a final product that is either longer or shorter than the corresponding DNA template. We develope an exclusion model for RNAP traffic where the kinetics of the system at the defect site captures key features of TS events. We demonstrate the interplay of the crowding of RNAPs and TS. A RNAP has to wait at the defect site for longer period in a more congested RNAP traffic, thereby increasing the likelihood of its suffering a larger number of TS events. The qualitative trends of some of our results for a simple special case of our model are consistent with experimental observations. The general theoretical framework presented here will be useful for guiding future experimental queries and for analysis of the experimental data with more detail
Long cell protrusions, which are effectively one-dimensional, are highly dynamic subcellular structures. Length of many such protrusions keep fluctuating about the mean value even in the the steady state. We develop here a stochastic model motivated by length fluctuations of a type of appendage of an eukaryotic cell called flagellum (also called cilium). Exploiting the techniques developed for the calculation of level-crossing statistics of random excursions of stochastic process, we have derived analytical expressions of passage times for hitting various thresholds, sojourn times of random excursions beyond the threshold and the extreme lengths attained during the lifetime of these model flagella. We identify different parameter regimes of this model flagellum that mimic those of the wildtype and mutants of a well known flagellated cell. By analysing our model in these different parameter regimes, we demonstrate how mutation can alter the level-crossing statistics even when the steady state length remains unaffected by the same mutation. Comparison of the theoretically predicted level crossing statistics, in addition to mean and variance of the length, in the steady state with the corresponding experimental data can be used in near future as stringent tests for the validity of the models of flagellar length control. The experimental data required for this purpose, though never reported till now, can be collected, in principle, using a method developed very recently for flagellar length fluctuations.
The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo and two membrane-bound SNARE pairs that specify fus ion and differ in their affinities for each type of vesicles. The mammalian Golgi complex is composed of 6-8 non-identical cisternae that undergo gradual maturation and replacement yet features only two SNARE pairs. We present a model that explains how the distinct composition of Golgi cisternae can be generated with two and even a single SNARE pair and one vesicle coat. A decay of active SNARE concentration in aging cisternae provides the seed for a cis > trans SNARE gradient that generates the predominantly retrograde vesicle flux which further enhances the gradient. This flux in turn yields the observed inhomogeneous steady-state distribution of Golgi enzymes, which compete with each other and with the SNAREs for incorporation into transport vesicles. We show analytically that the steady state SNARE concentration decays exponentially with the cisterna number. Numerical solutions of rate equations reproduce the experimentally observed SNARE gradients, overlapping enzyme peaks in cis, medial and trans and the reported change in vesicle nature across Golgi: Vesicles originating from younger cisternae mostly contain Golgi enzymes and SNAREs enriched in these cisternae and extensively recycle through the Endoplasmic Reticulum (ER), while the other subpopulation of vesicles contains Golgi proteins prevalent in older cisternae and hardly reaches the ER.
We study the dynamics of a simple adaptive system in the presence of noise and periodic damping. The system is composed by two paths connecting a source and a sink, the dynamics is governed by equations that usually describe food search of the paradi gmatic Physarum polycephalum. In this work we assume that the two paths undergo damping whose relative strength is periodically modulated in time and analyse the dynamics in the presence of stochastic forces simulating Gaussian noise. We identify different responses depending on the modulation frequency and on the noise amplitude. At frequencies smaller than the mean dissipation rate, the system tends to switch to the path which minimizes dissipation. Synchronous switching occurs at an optimal noise amplitude which depends on the modulation frequency. This behaviour disappears at larger frequencies, where the dynamics can be described by the time-averaged equations. Here, we find metastable patterns that exhibit the features of noise-induced resonances.
We present a study of exclusion processes on networks as models for complex transport phenomena and in particular for active transport of motor proteins along the cytoskeleton. We argue that active transport processes on networks spontaneously develo p density heterogeneities at various scales. These heterogeneities can be regulated through a variety of multi-scale factors, such as the interplay of exclusion interactions, the non-equilibrium nature of the transport process and the network topology. We show how an effective rate approach allows to develop an understanding of the stationary state of transport processes through complex networks from the phase diagram of one single segment. For exclusion processes we rationalize that the stationary state can be classified in three qualitatively different regimes: a homogeneous phase as well as inhomogeneous network and segment phases. In particular, we present here a study of the stationary state on networks of three paradigmatic models from non-equilibrium statistical physics: the totally asymmetric simple exclusion process, the partially asymmetric simple exclusion process and the totally asymmetric simple exclusion process with Langmuir kinetics. With these models we can interpolate between equilibrium (due to bi-directional motion along a network or infinite diffusion) and out-of-equilibrium active directed motion along a network. The study of these models sheds further light on the emergence of density heterogeneities in active phenomena.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا