scholarly journals In Silico Geobacter sulfurreducens Metabolism and Its Representation in Reactive Transport Models

2008 ◽  
Vol 75 (1) ◽  
pp. 83-92 ◽  
Author(s):  
E. L. King ◽  
K. Tuncay ◽  
P. Ortoleva ◽  
C. Meile
Keyword(s):  
Reactive Transport ◽  
Cell Model ◽  
Cell Metabolism ◽  
Growth Dynamics ◽  
Growth Efficiency ◽  
Geobacter Sulfurreducens ◽  
Balance Model ◽  
Substrate Uptake ◽  
Elemental Cycling ◽  
Dynamic Cell

ABSTRACT Microbial activity governs elemental cycling and the transformation of many anthropogenic substances in aqueous environments. Through the development of a dynamic cell model of the well-characterized, versatile, and abundant Geobacter sulfurreducens, we showed that a kinetic representation of key components of cell metabolism matched microbial growth dynamics observed in chemostat experiments under various environmental conditions and led to results similar to those from a comprehensive flux balance model. Coupling the kinetic cell model to its environment by expressing substrate uptake rates depending on intra- and extracellular substrate concentrations, two-dimensional reactive transport simulations of an aquifer were performed. They illustrated that a proper representation of growth efficiency as a function of substrate availability is a determining factor for the spatial distribution of microbial populations in a porous medium. It was shown that simplified model representations of microbial dynamics in the subsurface that only depended on extracellular conditions could be derived by properly parameterizing emerging properties of the kinetic cell model.

scholarly journals Stochasticity of cellular growth: sources, propagation and consequences

2018 ◽  
Author(s):  
Philipp Thomas ◽  
Guillaume Terradot ◽  
Vincent Danos ◽  
Andrea Y. Weiße
Keyword(s):  
Evolutionary Biology ◽  
Cell Model ◽  
Single Cells ◽  
Growth Dynamics ◽  
Cellular Growth ◽  
Bacterial Cells ◽  
Cell Processes ◽  
Cellular Machinery ◽  
Cross Correlations ◽  
Phenotypic Responses

Cellular growth impacts a range of phenotypic responses. Identifying the sources of fluctuations in growth and how they propagate across the cellular machinery can unravel mechanisms that underpin cell decisions. We present a stochastic cell model linking gene expression, metabolism and replication to predict growth dynamics in single bacterial cells. In addition to several population-averaged data, the model quantitatively recovers how growth fluctuations in single cells change across nutrient conditions. We develop a framework to analyse stochastic chemical reactions coupled with cell divisions and use it to identify sources of growth heterogeneity. By visualising cross-correlations we then determine how such initial fluctuations propagate to growth rate and affect other cell processes. We further study antibiotic responses and find that complex drug-nutrient interactions can both enhance and suppress heterogeneity. Our results provide a predictive framework to integrate single-cell and bulk data and draw testable predictions with implications for antibiotic tolerance, evolutionary biology and synthetic biology.

scholarly journals Geobacter sulfurreducens inner membrane cytochrome CbcBA controls electron transfer and growth yield near the energetic limit of respiration

2021 ◽  
Author(s):  
Komal Joshi ◽  
Chi Ho Chan ◽  
Daniel R. Bond
Keyword(s):  
Electron Transfer ◽  
Redox Potential ◽  
Growth Yield ◽  
Growth Efficiency ◽  
Geobacter Sulfurreducens ◽  
Redox Potentials ◽  
Hydrogen Electrode ◽  
Highly Expressed Genes ◽  
Reducing Bacteria ◽  
Transfer Chain

AbstractGeobacter sulfurreducens utilizes extracellular electron acceptors such as Mn(IV), Fe(III), syntrophic partners, and electrodes that vary from +0.4 to −0.3 V vs. Standard Hydrogen Electrode (SHE), representing a potential energy span that should require a highly branched electron transfer chain. Here we describe CbcBA, a bc-type cytochrome essential near the thermodynamic limit of respiration when acetate is the electron donor. Mutants lacking cbcBA ceased Fe(III) reduction at −0.21 V vs. SHE, could not transfer electrons to electrodes between −0.21 and −0.28 V, and could not reduce the final 10% – 35% of Fe(III) minerals. As redox potential decreased during Fe(III) reduction, cbcBA was induced with the aid of the regulator BccR to become one of the most highly expressed genes in G. sulfurreducens. Growth yield (CFU/mM Fe(II)) was 112% of WT in ΔcbcBA, and deletion of cbcL (a different bc-cytochrome essential near −0.15 V) in ΔcbcBA increased yield to 220%. Together with ImcH, which is required at high redox potentials, CbcBA represents a third cytoplasmic membrane oxidoreductase in G. sulfurreducens. This expanding list shows how these important metal-reducing bacteria may constantly sense redox potential to adjust growth efficiency in changing environments.

scholarly journals Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells

Metabolites ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 7 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V. Lee ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Cell Model ◽  
Cell Metabolism ◽  
Progression Free Survival ◽  
Central Carbon Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Disruption ◽  
Transcriptomic Changes

The aims of this study were to determine whether combination chemotherapeutics exhibit a synergistic effect on breast cancer cell metabolism. Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6, and when patients are treated in combination with fulvestrant, an estrogen receptor antagonist, they have improved progression-free survival. The mechanisms for this survival advantage are not known. Therefore, we analyzed metabolic and transcriptomic changes in MCF-7 cells following single and combination chemotherapy to determine whether selective metabolic pathways are targeted during these different modes of treatment. Individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy’s synergism in the cell model. This study also highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.

scholarly journals Ionic Charge Conservation and Long-Term Steady State in the Luo–Rudy Dynamic Cell Model

2001 ◽  
Vol 81 (6) ◽  
pp. 3324-3331 ◽  
Author(s):  
Thomas J. Hund ◽  
Jan P. Kucera ◽  
Niels F. Otani ◽  
Yoram Rudy
Keyword(s):  
Steady State ◽  
Cell Model ◽  
Ionic Charge ◽  
Charge Conservation ◽  
Dynamic Cell

scholarly journals Highly Glycolytic Immortalized Human Dermal Microvascular Endothelial Cells are Able to Grow in Glucose-Starved Conditions

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 332 ◽  
Author(s):  
Ocaña ◽  
Martínez-Poveda ◽  
Quesada ◽  
Medina
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Metabolism ◽  
Monocarboxylate Transporter ◽  
Microvascular Endothelial Cells ◽  
Substrate Uptake ◽  
Monocarboxylate Transporter 1 ◽  
Extracellular Lactate ◽  
Microvascular Endothelial ◽  
Reported Data

Endothelial cells form the inner lining of blood vessels, in a process known as angiogenesis. Excessive angiogenesis is a hallmark of several diseases, including cancer. The number of studies in endothelial cell metabolism has increased in recent years, and new metabolic targets for pharmacological treatment of pathological angiogenesis are being proposed. In this work, we wanted to address experimental evidence of substrate (namely glucose, glutamine and palmitate) dependence in immortalized dermal microvascular endothelial cells in comparison to primary endothelial cells. In addition, due to the lack of information about lactate metabolism in this specific type of endothelial cells, we also checked their capability of utilizing extracellular lactate. For fulfilling these aims, proliferation, migration, Seahorse, substrate uptake/utilization, and mRNA/protein expression experiments were performed. Our results show a high glycolytic capacity of immortalized dermal microvascular endothelial cells, but an early independence of glucose for cell growth, whereas a total dependence of glutamine to proliferate was found. Additionally, in contrast with reported data in other endothelial cell lines, these cells lack monocarboxylate transporter 1 for extracellular lactate incorporation. Therefore, our results point to the change of certain metabolic features depending on the endothelial cell line.

scholarly journals The miR-27a/FOXJ3 Axis Dysregulates Mitochondrial Homeostasis in Colorectal Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4994
Author(s):  
Giovannina Barisciano ◽  
Manuela Leo ◽  
Livio Muccillo ◽  
Erica Pranzini ◽  
Matteo Parri ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Cell Model ◽  
Mitochondrial Dynamics ◽  
Cell Metabolism ◽  
Xenograft Model ◽  
Mitochondrial Homeostasis ◽  
Mouse Xenograft Model ◽  
Cell Model System

miR-27a plays a driver role in rewiring tumor cell metabolism. We searched for new miR-27a targets that could affect mitochondria and identified FOXJ3, an apical factor of mitochondrial biogenesis. We analyzed FOXJ3 levels in an in vitro cell model system that was genetically modified for miR-27a expression and validated it as an miR-27a target. We showed that the miR-27a/FOXJ3 axis down-modulates mitochondrial biogenesis and other key members of the pathway, implying multiple levels of control. As assessed by specific markers, the miR-27a/FOXJ3 axis also dysregulates mitochondrial dynamics, resulting in fewer, short, and punctate organelles. Consistently, in high miR-27a-/low FOXJ3-expressing cells, mitochondria are functionally characterized by lower superoxide production, respiration capacity, and membrane potential, as evaluated by OCR assays and confocal microscopy. The analysis of a mouse xenograft model confirmed FOXJ3 as a target and suggested that the miR-27a/FOXJ3 axis affects mitochondrial abundance in vivo. A survey of the TCGA-COADREAD dataset supported the inverse relationship of FOXJ3 with miR-27a and reinforced cellular component organization or biogenesis as the most affected pathway. The miR-27a/FOXJ3 axis acts as a central hub in regulating mitochondrial homeostasis. Its discovery paves the way for new therapeutic strategies aimed at restraining tumor growth by targeting mitochondrial activities.

A dynamic cell model for the formation of epithelial tissues

2001 ◽  
Vol 81 (7) ◽  
pp. 699-719 ◽  
Author(s):  
Tatsuzo Nagai ◽  
Hisao Honda
Keyword(s):  
Cell Model ◽  
Epithelial Tissues ◽  
Dynamic Cell

scholarly journals Sequential Parameter Estimation for Mammalian Cell Model Based on In Silico Design of Experiments

Processes ◽  
2018 ◽  
Vol 6 (8) ◽  
pp. 100 ◽  
Author(s):  
Zhenyu Wang ◽  
Hana Sheikh ◽  
Kyongbum Lee ◽  
Christos Georgakis
Keyword(s):  
Parameter Estimation ◽  
Mammalian Cells ◽  
Cell Model ◽  
Cell Metabolism ◽  
Model Performance ◽  
Sequential Estimation ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Algebraic Equations ◽  
Estimation Of Parameters

Due to the complicated metabolism of mammalian cells, the corresponding dynamic mathematical models usually consist of large sets of differential and algebraic equations with a large number of parameters to be estimated. On the other hand, the measured data for estimating the model parameters are limited. Consequently, the parameter estimates may converge to a local minimum far from the optimal ones, especially when the initial guesses of the parameter values are poor. The methodology presented in this paper provides a systematic way for estimating parameters sequentially that generates better initial guesses for parameter estimation and improves the accuracy of the obtained metabolic model. The model parameters are first classified into four subsets of decreasing importance, based on the sensitivity of the model’s predictions on the parameters’ assumed values. The parameters in the most sensitive subset, typically a small fraction of the total, are estimated first. When estimating the remaining parameters with next most sensitive subset, the subsets of parameters with higher sensitivities are estimated again using their previously obtained optimal values as the initial guesses. The power of this sequential estimation approach is illustrated through a case study on the estimation of parameters in a dynamic model of CHO cell metabolism in fed-batch culture. We show that the sequential parameter estimation approach improves model accuracy and that using limited data to estimate low-sensitivity parameters can worsen model performance.

Unique and Shared Metabolic Regulation in Clonal β-Cells and Primary Islets Derived From Rat Revealed by Metabolomics Analysis

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 1995-2005 ◽  
Author(s):  
Peter Spégel ◽  
Lotta E. Andersson ◽  
Petter Storm ◽  
Vladimir Sharoyko ◽  
Isabel Göhring ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Cell Model ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Cellular Heterogeneity ◽  
Β Cells ◽  
Β Cell ◽  
Rat Islets ◽  
Altered Glucose ◽  
Elevated Glucose

Abstract As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell population stressed by the islet isolation procedure, whereas rat-derived clonal β-cells exhibit a tumor-like phenotype. To describe to what extent either of these models reflect normal cellular metabolism, we compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used clonal β-cell model. We found that insulin secretion and metabolic regulation provoked by glucose were qualitatively similar in these β-cell models. However, rat islets exhibited a more pronounced glucose-provoked increase of glutamate, glycerol-3-phosphate, succinate, and lactate levels, whereas INS-1 832/13 cells showed a higher glucose-elicited increase in glucose-6-phosphate, alanine, isocitrate, and α-ketoglutarate levels. Glucose induced a decrease in levels of γ-aminobutyrate (GABA) and aspartate in rat islets and INS-1 832/13 cells, respectively. Genes with cellular functions related to proliferation and the cell cycle were more highly expressed in the INS-1 832/13 cells. Most metabolic pathways that were differentially expressed included GABA metabolism, in line with altered glucose responsiveness of GABA. Also, lactate dehydrogenase A, which is normally expressed at low levels in mature β-cells, was more abundant in rat islets than in INS-1 832/13 cells, confirming the finding of elevated glucose-provoked lactate production in the rat islets. Overall, our results suggest that metabolism in rat islets and INS-1 832/13 cells is qualitatively similar, albeit with quantitative differences. Differences may be accounted for by cellular heterogeneity of islets and proliferation of the INS-1 832/13 cells.

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