Publications by authors named "Atul Narang"

The expression of recombinant proteins by the promoter of is typically induced by adding methanol to the cultivation medium. Since growth on methanol imposes a high oxygen demand, the medium is often supplemented with an additional secondary carbon source which serves to reduce the consumption of methanol, and hence, oxygen. Early research recommended the use of glycerol as the secondary carbon source, but more recent studies recommend the use of sorbitol because glycerol represses P expression.

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The lac operon of Escherichia coli is repressed several 100-fold in the presence of glucose. This repression has been attributed to cAMP receptor protein-mediated inhibition of lac transcription and EIIA-mediated inhibition of lactose transport (inducer exclusion). The growing evidence against the first mechanism has led to the postulate that the repression is driven by inducer exclusion.

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The expression of the lac operon of E. coli is subject to positive feedback during growth in the presence of gratuitous inducers, but its existence in the presence of lactose remains controversial. The key question in this debate is: Do the lactose enzymes, Lac permease and β-galactosidase, promote accumulation of allolactose? If so, positive feedback exists since allolactose does stimulate synthesis of the lactose enzymes.

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The methylotrophic yeast Komagataella phaffii is among the most popular hosts for recombinant protein synthesis. Most recombinant proteins have been expressed in the wild-type Mut host strain from the methanol-inducible alcohol oxidase (AOX) promoter P. Since methanol metabolism has undesirable consequences, two additional host strains, Mut (Δaox1) and Mut (Δaox1Δaox2), were introduced which consume less methanol and reportedly also express recombinant protein better than Mut.

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Fitting the probability mass functions from analytical solutions of stochastic models of gene expression to the single-cell count distributions of mRNA and protein molecules can yield valuable insights into mechanisms underlying gene expression. Solutions of chemical master equations are available for various kinetic schemes but, even for the basic ON-OFF genetic switch, they take complex forms with generating functions given as hypergeometric functions. Interpretation of gene expression dynamics in terms of bursts is not consistent with the complete range of parameters for these functions.

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Mechanistic models of stochastic gene expression are of considerable interest, but their complexity often precludes tractable analytical expressions for messenger RNA (mRNA) and protein distributions. The lac operon of Escherichia coli is a model system with regulatory elements such as multiple operators and DNA looping that are shared by many operons. Although this system is complex, intuition suggests that fast DNA looping may simplify it by causing the repressor-bound states of the operon to equilibrate rapidly, thus ensuring that the subsequent dynamics are governed by slow transitions between the repressor-free and the equilibrated repressor-bound states.

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Background: Recently, we showed that steady-state continuous cultures of   follow the principles of growth on mixture of two complementary substrates. More precisely, when such cultures are fed with progressively higher concentrations of glucose at fixed dilution rate  = 0.1 h, oxygen mass-transfer coefficient  = 50 h, and oxygen solubility , they transition from glucose- to oxygen-limited growth through an intermediate dual-limited regime in which both glucose and oxygen are limiting, and ethanol is produced without loss of glucose.

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Under aerobic conditions, Crabtree-negative yeasts grow but do not ferment, and under anaerobic conditions, they ferment but do not grow. It is therefore believed that fermentation by these yeasts is sensitive to small variations of the operating parameters, e.g.

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The (lactose) operon (which processes β-galactosides) and the (melibiose) operon (which processes α-galactosides) of have a close historical connection. A number of shared substrates and effectors of the permeases and regulatory proteins have been reported over the years. Until now, β-thiogalactosides like TMG (methyl-β-d-thiogalactopyranoside) and IPTG (isopropyl-β-d-thiogalactopyranoside) have not generally been considered to be inducers of the operon.

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Although noisy gene expression is widely accepted, its mechanisms are subjects of debate, stimulated largely by single-molecule experiments. This work is concerned with one such study, in which Choi et al., 2008, obtained real-time data and distributions of Lac permease in E.

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Background: Most modelling efforts of transcriptional networks involve estimations of in vivo concentrations of components, binding affinities and reaction rates, derived from in vitro biochemical assays. These assays are difficult and in vitro measurements may not approximate actual in vivo conditions. Alternatively, changes in transcription factor activity can be estimated by using partially specified models which estimate the "hidden functions" of transcription factor concentration changes; however, non-unique solutions are a potential problem.

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Cyclic adenosine 5'-phosphate (cAMP) is a global regulator of gene expression in Escherichia coli. Despite decades of intensive study, the quantitative effect and regulatory function of cAMP remain the subjects of considerable debate. Here, we analyse the data in the literature to show that: (a) In carbon-limited cultures (including cultures limited by glucose), cAMP is at near-saturation levels with respect to expression of several catabolic promoters (including lac, ara and gal).

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During batch growth on mixtures of two growth-limiting substrates, microbes consume the substrates either sequentially (diauxie) or simultaneously. The ubiquity of these growth patterns suggests that they may be driven by a universal mechanism common to all microbial species. Recently, we showed that a minimal model accounting only for enzyme induction and dilution, the two processes that occur in all microbes, explains the phenotypes observed in batch cultures of various wild-type and mutant/recombinant cells (Narang and Pilyugin in J.

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In the presence of gratuitous inducers, the lac operon of Escherichia coli exhibits bistability. Most models in the literature assume that the inducer enters the cell via the carrier (permease), and exits by a diffusion-like process. The diffusive influx and carrier efflux are neglected.

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It is well known that in fMLP-stimulated neutrophils, phosphatidyl inositol 3,4,5-trisphosphate [PI(3,4,5)P3] localizes at the leading edge of the cells. However, no effort has been made to study the PI 4,5-bisphosphate [PI(4,5)P2] distribution in these cells. In fact, it has been suggested that PI(4,5)P2 is unlikely to localize, as its basal level is orders of magnitude higher than that of PI(3,4,5)P3.

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The lac operon of Escherichia coli can exhibit bistability. Early studies showed that bistability occurs during growth on TMG/succinate and lactose+glucose, but not during growth on lactose. More recently, studies with lacGFP-transfected cells show bistability during growth on TMG/succinate, but not during growth on lactose and lactose+glucose.

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Long-wavelength thermal fluctuations of lipid membranes are adequately described by the Helfrich elastic model. On the other hand, fluctuations of wavelengths comparable with bilayer thickness exhibit significant deviations from the prediction of the elastic model and are typically assumed to be dominated by microscopic surface tension due to protrusion of lipid molecules into the solvent. We present evidence that the short-wavelength modes of a lipid membrane are dominated by fluctuations of the tilt of lipid molecules with respect to the membrane normal rather than the microscopic surface tension.

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The mechanisms that mediate biomembrane shape transformations are of considerable interest in cell biology. Recent in vitro experiments show that the chemical transformation of minor membrane lipids can induce dramatic shape changes in biomembranes. Specifically, it was observed that the addition of DOPA to DOPE has no effect on the stability of the bilayer structure of the membrane.

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The induction of the lac operon follows cooperative kinetics. The first mechanistic model of these kinetics is the de facto standard in the modeling literature [Yagil, G., Yagil, E.

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When bacteria are grown in a batch culture containing a mixture of two growth-limiting substrates, they exhibit a rich spectrum of substrate consumption patterns including diauxic growth, simultaneous consumption, and bistable growth. In previous work, we showed that a minimal model accounting only for enzyme induction and dilution captures all the substrate consumption patterns [Narang, A., 1998a.

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Mixed-substrate microbial growth is of fundamental interest in microbiology and bioengineering. Several mathematical models have been developed to account for the genetic regulation of such systems, especially those resulting in diauxic growth. In this work, we compare the dynamics of three such models (Narang, 1998a.

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A key problem of eukaryotic cell motility is the signaling mechanism of chemoattractant gradient sensing. Recent experiments have revealed the molecular correlate of gradient sensing: Frontness molecules, such as PI3P and Rac, localize at the front end of the cell, and backness molecules, such as Rho and myosin II, accumulate at the back of the cell. Importantly, this frontness-backness polarization occurs spontaneously even if the cells are exposed to uniform chemoattractant profiles.

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We present a model for diauxic growth of denitrifying bacteria in which nitrate reductase synthesis kinetics dominate the overall growth kinetics. The model is based on the assumption of the existence of a nitrate respiration operon, thereby linking the rate of nitrate uptake to the activity of nitrate reductase. We show that this approach can model diauxic growth of Pseudomonas denitrificans by conducting experiments in which nitrate reductase activity was measured during both lag and ensuing exponential growth phases.

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