scholarly journals E. colitranslation strategies differ across nutrient conditions

2018 ◽  
Author(s):  
Sophia Hsin-Jung Li ◽  
Zhiyuan Li ◽  
Junyoung O. Park ◽  
Christopher G. King ◽  
Joshua D. Rabinowitz ◽  
...  
Keyword(s):  
Growth Rate ◽  
Linear Relationship ◽  
Production Rate ◽  
Protein Production ◽  
Growth Conditions ◽  
Nucleic Acid Metabolism ◽  
P Limitation ◽  
Enhance Protein Synthesis ◽  
Optimal Resource ◽  
Protein Production Rate

AbstractFor cells to grow faster they must increase their protein production rate. Microorganisms have traditionally been thought to accomplish this increase by producing more ribosomes to enhance protein synthesis capacity, leading to the linear relationship between ribosome level and growth rate observed under most growth conditions previously examined. Past studies have suggested that this linear relationship represents an optimal resource allocation strategy for each growth rate, independent of any specific nutrient state. Here we investigate protein production strategies in continuous cultures limited for carbon, nitrogen, and phosphate, which differentially impact substrate supply for protein versus nucleic acid metabolism. Unexpectedly, we find that at slow growth rates,E. coliachieves the same protein production rate using three different strategies under the three different nutrient limitations. Upon phosphate (P) limitation, translation is slow due to a particularly low abundance of ribosomes, which are RNA-rich and thus particularly costly for phosphorous-limited cells. In nitrogen (N) limitation, translation is slowed by limited glutamine and stalling at glutamine codons, resulting is slow elongation. In carbon (C) limitation, translation is slowed by accumulation of inactive ribosomes not bound to mRNA. These extra ribosomes enable rapid growth acceleration upon nutrient upshift. Thus, bacteria tune ribosome usage across different limiting nutrients to enable balanced nutrient-limited growth while also preparing for future nutrient upshifts.

scholarly journals Maximizing protein translation rate in the non-homogeneous ribosome flow model: a convex optimization approach

2014 ◽  
Vol 11 (100) ◽  
pp. 20140713 ◽  
Author(s):  
Gilad Poker ◽  
Yoram Zarai ◽  
Michael Margaliot ◽  
Tamir Tuller
Keyword(s):  
Synthetic Biology ◽  
Convex Optimization ◽  
Production Rate ◽  
Protein Production ◽  
Flow Model ◽  
Protein Translation ◽  
Optimization Approach ◽  
Initiation Rate ◽  
Translation Rate ◽  
Protein Production Rate

Translation is an important stage in gene expression. During this stage, macro-molecules called ribosomes travel along the mRNA strand linking amino acids together in a specific order to create a functioning protein. An important question, related to many biomedical disciplines, is how to maximize protein production. Indeed, translation is known to be one of the most energy-consuming processes in the cell, and it is natural to assume that evolution shaped this process so that it maximizes the protein production rate. If this is indeed so then one can estimate various parameters of the translation machinery by solving an appropriate mathematical optimization problem. The same problem also arises in the context of synthetic biology, namely, re-engineer heterologous genes in order to maximize their translation rate in a host organism. We consider the problem of maximizing the protein production rate using a computational model for translation–elongation called the ribosome flow model (RFM). This model describes the flow of the ribosomes along an mRNA chain of length n using a set of n first-order nonlinear ordinary differential equations. It also includes n + 1 positive parameters: the ribosomal initiation rate into the mRNA chain, and n elongation rates along the chain sites. We show that the steady-state translation rate in the RFM is a strictly concave function of its parameters. This means that the problem of maximizing the translation rate under a suitable constraint always admits a unique solution, and that this solution can be determined using highly efficient algorithms for solving convex optimization problems even for large values of n . Furthermore, our analysis shows that the optimal translation rate can be computed based only on the optimal initiation rate and the elongation rate of the codons near the beginning of the ORF. We discuss some applications of the theoretical results to synthetic biology, molecular evolution, and functional genomics.

scholarly journals Ribosome flow model with extended objects

2017 ◽  
Vol 14 (135) ◽  
pp. 20170128 ◽  
Author(s):  
Yoram Zarai ◽  
Michael Margaliot ◽  
Tamir Tuller
Keyword(s):  
Steady State ◽  
Production Rate ◽  
Protein Production ◽  
Flow Model ◽  
Mean Field ◽  
State Density ◽  
Transition Rates ◽  
Ribosome Density ◽  
Protein Production Rate ◽  
Unique Steady State

We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called the ribosome flow model with extended objects  (RFMEO). This model encapsulates many realistic features of translation including non-homogeneous transition rates along mRNA, the fact that every ribosome covers several codons, and the fact that ribosomes cannot overtake one another. The RFMEO is a mean-field approximation of an important model from statistical mechanics called the totally asymmetric simple exclusion process with extended objects (TASEPEO). We demonstrate that the RFMEO describes biophysical aspects of translation better than previous mean-field approximations, and that its predictions correlate well with those of TASEPEO. However, unlike TASEPEO, the RFMEO is amenable to rigorous analysis using tools from systems and control theory. We show that the ribosome density profile along the mRNA in the RFMEO converges to a unique steady-state density that depends on the length of the mRNA, the transition rates along it, and the number of codons covered by every ribosome, but not on the initial density of ribosomes along the mRNA. In particular, the protein production rate also converges to a unique steady state. Furthermore, if the transition rates along the mRNA are periodic with a common period  T then the ribosome density along the mRNA and the protein production rate converge to a unique periodic pattern with period  T , that is, the model entrains to periodic excitations in the transition rates. Analysis and simulations of the RFMEO demonstrate several counterintuitive results. For example, increasing the ribosome footprint may sometimes lead to an increase in the production rate. Also, for large values of the footprint the steady-state density along the mRNA may be quite complex (e.g. with quasi-periodic patterns) even for relatively simple (and non-periodic) transition rates along the mRNA. This implies that inferring the transition rates from the ribosome density may be non-trivial. We believe that the RFMEO could be useful for modelling, understanding and re-engineering translation as well as other important biological processes.

scholarly journals Correlation of gene expression and protein production rate - a system wide study

BMC Genomics ◽  
2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Mikko Arvas ◽  
Tiina Pakula ◽  
Bart Smit ◽  
Jari Rautio ◽  
Heini Koivistoinen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Production Rate ◽  
Protein Production ◽  
Protein Production Rate

scholarly journals Deciphering mRNA Sequence Determinants of Protein Production Rate

2018 ◽  
Vol 120 (12) ◽  
Author(s):  
Juraj Szavits-Nossan ◽  
Luca Ciandrini ◽  
M. Carmen Romano
Keyword(s):  
Production Rate ◽  
Protein Production ◽  
Mrna Sequence ◽  
Protein Production Rate

Controlling translation elongation efficiency: tRNA regulation of ribosome flux on the mRNA

2014 ◽  
Vol 42 (1) ◽  
pp. 160-165 ◽  
Author(s):  
Barbara Gorgoni ◽  
Elizabeth Marshall ◽  
Matthew R. McFarland ◽  
M. Carmen Romano ◽  
Ian Stansfield
Keyword(s):  
Gene Expression ◽  
Production Rate ◽  
Protein Production ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Translation Elongation ◽  
Control Of Gene Expression ◽  
Holistic Understanding ◽  
Predictive Understanding ◽  
Protein Production Rate

Gene expression can be regulated by a wide variety of mechanisms. One example concerns the growing body of evidence that the protein-production rate can be regulated at the level of translation elongation by controlling ribosome flux across the mRNA. Variations in the abundance of tRNA molecules cause different rates of translation of their counterpart codons. This, in turn, produces a variable landscape of translational rate across each and every mRNA, with the dynamic formation and deformation of ribosomal queues being regulated by both tRNA availability and the rates of translation initiation and termination. In the present article, a range of examples of tRNA control of gene expression are reviewed, and the use of mathematical modelling to develop a predictive understanding of the consequences of that regulation is discussed and explained. These findings encourage a view that predicting the protein-synthesis rate of each mRNA requires a holistic understanding of how each stage of translation, including elongation, contributes to the overall protein-production rate.

scholarly journals Phosphorus stress induces the synthesis of novel glycolipids in Pseudomonas aeruginosa that confer protection against a last-resort antibiotic

2021 ◽  
Author(s):  
Rebekah A. Jones ◽  
Holly Shropshire ◽  
Caimeng Zhao ◽  
Andrew Murphy ◽  
Ian Lidbury ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Sensitivity ◽  
Polymyxin B ◽  
Growth Conditions ◽  
Membrane Lipid ◽  
Comparative Genomic ◽  
P Limitation ◽  
Lung Microbiome ◽  
Glycolipid Synthesis

AbstractPseudomonas aeruginosa is a nosocomial pathogen with a prevalence in immunocompromised individuals and is particularly abundant in the lung microbiome of cystic fibrosis patients. A clinically important adaptation for bacterial pathogens during infection is their ability to survive and proliferate under phosphorus-limited growth conditions. Here, we demonstrate that P. aeruginosa adapts to P-limitation by substituting membrane glycerophospholipids with sugar-containing glycolipids through a lipid renovation pathway involving a phospholipase and two glycosyltransferases. Combining bacterial genetics and multi-omics (proteomics, lipidomics and metatranscriptomic analyses), we show that the surrogate glycolipids monoglucosyldiacylglycerol and glucuronic acid-diacylglycerol are synthesised through the action of a new phospholipase (PA3219) and two glycosyltransferases (PA3218 and PA0842). Comparative genomic analyses revealed that this pathway is strictly conserved in all P. aeruginosa strains isolated from a range of clinical and environmental settings and actively expressed in the metatranscriptome of cystic fibrosis patients. Importantly, this phospholipid-to-glycolipid transition comes with significant ecophysiological consequence in terms of antibiotic sensitivity. Mutants defective in glycolipid synthesis survive poorly when challenged with polymyxin B, a last-resort antibiotic for treating multi-drug resistant P. aeruginosa. Thus, we demonstrate an intriguing link between adaptation to environmental stress (nutrient availability) and antibiotic resistance, mediated through membrane lipid renovation that is an important new facet in our understanding of the ecophysiology of this bacterium in the lung microbiome of cystic fibrosis patients.

Preparation and characterization of epitaxial iron oxide films

1998 ◽  
Vol 13 (7) ◽  
pp. 2003-2014 ◽  
Author(s):  
Y. Gao ◽  
Y. J. Kim ◽  
S. A. Chambers
Keyword(s):  
Growth Rate ◽  
Iron Oxide ◽  
Oxygen Plasma ◽  
Film Surface ◽  
Surface Region ◽  
Growth Conditions ◽  
Epitaxial Films ◽  
Pure Phase ◽  
Iron Oxide Films

Well-ordered, pure-phase epitaxial films of FeO, Fe3O4, and γ–Fe2O3 were prepared on MgO(001) by oxygen-plasma-assisted MBE. The stoichiometries of these thin films were controlled by varying the growth rate and oxygen partial pressure. Selective growth of γ–Fe2O3 and α–Fe2O3 was achieved by controlling the growth conditions in conjunction with the choice of appropriate substrates. Growth of the iron oxide epitaxial films on MgO at ≥350 °C is accompanied by significant Mg outdiffusion. The FeO(001) film surface exhibits a (2 × 2) reconstruction, which is accompanied by a significant amount of Fe3+ in the surface region. Fe3O4 (001) has been found to reconstruct to a structure. γ–Fe23 (001) film surface is unreconstructed.

Emission characteristics of GaInN/GaN multiple quantum shell nanowire-based LEDs with different p-GaN growth conditions

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sae Katsuro ◽  
Weifang Lu ◽  
Kazuma Ito ◽  
Nanami Nakayama ◽  
Naoki Sone ◽  
...  
Keyword(s):  
Growth Rate ◽  
Shell Growth ◽  
Light Output ◽  
High Growth ◽  
Growth Conditions ◽  
High Growth Rate ◽  
Current Injection ◽  
Emission Characteristics ◽  
Multiple Quantum ◽  
Plane Region

Abstract Improving current injection into r- and m-planes of nanowires (NWs) is essential to realizing efficient GaInN/GaN multiple quantum shell (MQS) NW-based light-emitting diodes (LEDs). Here, we present the effects of different p-GaN shell growth conditions on the emission characteristics of MQS NW-LEDs. Firstly, a comparison between cathodoluminescence (CL) and electroluminescence (EL) spectra indicates that the emission in NW-LEDs originates from the top region of the NWs. By growing thick p-GaN shells, the variable emission peak at around 600 nm and degradation of the light output of the NW-LEDs are elaborated, which is attributable to the localization of current in the c-plane region with various In-rich clusters and deep-level defects. Utilizing a high growth rate of p-GaN shell, an increased r-plane and a reduced c-plane region promote the deposition of indium tin oxide layer over the entire NW. Therefore, the current is effectively injected into both the r- and m-planes of the NW structures. Consequently, the light output and EL peak intensity of the NW-LEDs are enhanced by factors of 4.3 and 13.8, respectively, under an injection current of 100 mA. Furthermore, scanning transmission electron microscope images demonstrate the suppression of dislocations, triangular defects, and stacking faults at the apex of the p-GaN shell with a high growth rate. Therefore, localization of current injection in nonradiative recombination centers near the c-plane was also inhibited. Our results emphasize the possibility of realizing high efficacy in NW-LEDs via optimal p-GaN shell growth conditions, which is quite promising for application in the long-wavelength region.

scholarly journals Massive Phenotypic Measurements Reveal Complex Physiological Consequences of Differential Translation Efficacies

2017 ◽  
Author(s):  
Adam Paul Arkin ◽  
Guillaume Cambray
Keyword(s):  
Growth Rate ◽  
Translation Initiation ◽  
Protein Production ◽  
Protein Biosynthesis ◽  
Cellular Growth ◽  
Sequence Variants ◽  
Release Rates ◽  
Trade Offs ◽  
Fluctuating Environments ◽  
Protein Overproduction

ABSTRACTControl of protein biosynthesis is at the heart of resource allocation and cell adaptation to fluctuating environments. One gene’s translation often occurs at the expense of another’s, resulting in global energetic and fitness trade-offs during differential expression of various functions. Patterns of ribosome utilization—as controlled by initiation, elongation and release rates—are central to this balance. To disentangle their respective determinants and physiological impacts, we complemented measurements of protein production with highly parallelized quantifications of transcripts’ abundance and decay, ribosome loading and cellular growth rate for 244,000 precisely designed sequence variants of an otherwise standard reporter. We find highly constrained, non-monotonic relationships between measured phenotypes. We show that fitness defects derive either from protein overproduction, with efficient translation initiation and heavy ribosome flows; or from unproductive ribosome sequestration by highly structured, slowly initiated and overly stabilized transcripts. These observations demonstrate physiological impacts of key sequence features in natural and designed transcripts.

scholarly journals <sup>210</sup>Pb-<sup>226</sup>Ra chronology reveals rapid growth rate of <i>Madrepora oculata</I> and <i>Lophelia pertusa</i> on world's largest cold-water coral reef

2011 ◽  
Vol 8 (6) ◽  
pp. 12247-12283
Author(s):  
P. Sabatier ◽  
J.-L. Reyss ◽  
J. M. Hall-Spencer ◽  
C. Colin ◽  
N. Frank ◽  
...  
Keyword(s):  
Growth Rate ◽  
Coral Reef ◽  
Linear Growth ◽  
Cold Water ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Age And Growth ◽  
Linear Growth Rate ◽  
Lophelia Pertusa ◽  
Water Coral

Abstract. Here we show the use of the 210Pb-226Ra excess method to determine the growth rate of corals from one of the world's largest known cold-water coral reef, the Røst Reef off Norway. Two large branching framework-forming cold-water coral specimens, one Lophelia pertusa and one Madrepora oculata were collected alive at 350 m water depth from the Røst Reef at ~67° N and ~9° E. Pb and Ra isotopes were measured along the major growth axis of both specimens using low level alpha and gamma spectrometry and the corals trace element compositions were studied using ICP-QMS. Due to the different chemical behaviors of Pb and Ra in the marine environment, 210Pb and 226Ra were not incorporated the same way into the aragonite skeleton of those two cold-water corals. Thus to assess of the growth rates of both specimens we have here taken in consideration the exponential decrease of initially incorporated 210Pb as well as the ingrowth of 210Pb from the decay of 226Ra. Moreover a~post-depositional 210Pb incorporation is found in relation to the Mn-Fe coatings that could not be entirely removed from the oldest parts of the skeletons. The 226Ra activities in both corals were fairly constant, then assuming constant uptake of 210Pb through time the 210Pb-226Ra chronology can be applied to calculate linear growth rate. The 45.5 cm long branch of M. oculata reveals an age of 31 yr and a~linear growth rate of 14.4 ± 1.1 mm yr−1, i.e. 2.6 polyps per year. However, a correction regarding a remaining post-depositional Mn-Fe oxide coating is needed for the base of the specimen. The corrected age tend to confirm the radiocarbon derived basal age of 40 yr (using 14C bomb peak) with a mean growth rate of 2 polyps yr−1. This rate is similar to the one obtained in Aquaria experiments under optimal growth conditions. For the 80 cm-long specimen of L. pertusa a remaining contamination of metal-oxides is observed for the middle and basal part of the coral skeleton, inhibiting similar accurate age and growth rate estimates. However, the youngest branch was free of Mn enrichment and this 15 cm section reveals a growth rate of 8 mm yr−1 (~1 polyp every two to three years). However, the 210Pb growth rate estimate is within the lowermost ranges of previous growth rate estimates and may thus reflect that the coral was not developing at optimal growth conditions. Overall, 210Pb-226Ra dating can be successfully applied to determine the age and growth rate of framework-forming cold-water corals, however, removal of post-depositional Mn-Fe oxide deposits is a prerequisite. If successful, large branching M. oculata and L. pertusa coral skeletons provide unique oceanographic archive for studies of intermediate water environmentals with an up to annual time resolution and spanning over many decades.

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