Determination of the Gene Regulatory Network of a Genome-Reduced Bacterium Highlights Alternative Regulation Independent of Transcription Factors.

Cell Syst. 2019 Aug 06;:

Authors: Yus E, Lloréns-Rico V, Martínez S, Gallo C, Eilers H, Blötz C, Stülke J, Lluch-Senar M, Serrano L

Abstract
Here, we determined the relative importance of different transcriptional mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae, by employing an array of experimental techniques under multiple genetic and environmental perturbations. Of the 143 genes tested (21% of the bacterium's annotated proteins), only 55% showed an altered phenotype, highlighting the robustness of biological systems. We identified nine transcription factors (TFs) and their targets, representing 43% of the genome, and 16 regulators that indirectly affect transcription. Only 20% of transcriptional regulation is mediated by canonical TFs when responding to perturbations. Using a Random Forest, we quantified the non-redundant contribution of different mechanisms such as supercoiling, metabolic control, RNA degradation, and chromosome topology to transcriptional changes. Model-predicted gene changes correlate well with experimental data in 95% of the tested perturbations, explaining up to 70% of the total variance when also considering noise. This analysis highlights the importance of considering non-TF-mediated regulation when engineering bacteria.

PMID: 31445891 [PubMed - as supplied by publisher]

How preparation and preservation procedures affect the properties of amniotic membrane? How safe are the procedures?

Burns. 2019 Aug 21;:

Authors: Gholipourmalekabadi M, Farhadihosseinabadi B, Faraji M, Nourani MR

Abstract
Human amniotic membrane (AM) has been widely used for tissue engineering and regenerative medicine applications. AM has many favorable characteristics such as high biocompatibility, antibacterial activity, anti-scarring property, immunomodulatory effects, anti-cancer behavior and contains several growth factors that make it an excellent natural candidate for wound healing. To date, various methods have been developed to prepare, preserve, cross-link and sterilize the AM. These methods remarkably affect the morphological, physico-chemical and biological properties of AM. Optimization of an effective and safe method for preparation and preservation of AM for a specific application is critical. In this review, the isolation, different methods of preparation, preservation, cross-linking and sterilization as well as their effects on properties of AM are well discussed. For each section, at least one effective and safe protocol is described in detail.

PMID: 31445711 [PubMed - as supplied by publisher]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/08/25

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"systems biology"

These pubmed results were generated on 2019/08/24

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"systems biology"

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"systems biology"

These pubmed results were generated on 2019/08/23

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"systems biology"

These pubmed results were generated on 2019/08/23

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"systems biology"

These pubmed results were generated on 2019/08/22

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"systems biology"

These pubmed results were generated on 2019/08/21

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"systems biology"

These pubmed results were generated on 2019/08/20

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"systems biology"

These pubmed results were generated on 2019/08/17

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"systems biology"

These pubmed results were generated on 2019/08/17

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"systems biology"

These pubmed results were generated on 2019/08/16

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"systems biology"

These pubmed results were generated on 2019/08/15

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"systems biology"

These pubmed results were generated on 2019/08/14

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A generalized computational framework to streamline thermodynamics and kinetics analysis of metabolic pathways.

Metab Eng. 2019 Aug 08;:

Authors: Wu C, Jiang H, Kalra I, Wang X, Cano M, Maness P, Yu J, Xiong W

Abstract
Metabolic engineering is a critical biotechnological approach in addressing global energy and environment challenges. Most engineering efforts, however, consist of laborious and inefficient trial-and-error of target pathways, due in part to the lack of methodologies that can comprehensively assess pathway properties in thermodynamics and kinetics. Metabolic engineering can benefit from computational tools that evaluate feasibility, expense and stability of non-natural metabolic pathways. Such tools can also help us understand natural pathways and their regulation at systems level. Here we introduce a computational toolbox, PathParser, which, for the first time, integrates multiple important functions for pathway analysis including thermodynamics analysis, kinetics-based protein cost optimization and robustness analysis. Specifically, PathParser enables optimization of the driving force of a pathway by minimizing the Gibbs free energy of least thermodynamically favorable reaction. In addition, based on reaction thermodynamics and enzyme kinetics, it can compute the minimal enzyme protein cost that supports metabolic flux, and evaluate pathway stability and flux in response to enzyme concentration perturbations. In a demo analysis of the Calvin-Benson-Bassham cycle and photorespiration pathway in the model cyanobacterium Synechocystis PCC 6803, the computation results are corroborated by experimental proteomics data as well as metabolic engineering outcomes. This toolbox may have broad application in metabolic engineering and systems biology in other microbial systems.

PMID: 31401243 [PubMed - as supplied by publisher]

Computational Insights into Avidity of Polymeric Multivalent Binders.

Biophys J. 2019 Jul 24;:

Authors: Zumbro E, Witten J, Alexander-Katz A

Abstract
Multivalent binding interactions are commonly found throughout biology to enhance weak monovalent binding such as between glycoligands and protein receptors. Designing multivalent polymers to bind to viruses and toxic proteins is a promising avenue for inhibiting their attachment and subsequent infection of cells. Several studies have focused on oligomeric multivalent inhibitors and how changing parameters such as ligand shape, size, linker length, and flexibility affect binding. However, experimental studies of how larger structural parameters of multivalent polymers, such as degree of polymerization, affect binding avidity to targets have mixed results, with some finding an improvement with longer polymers and some finding no effect. Here, we use Brownian dynamics simulations to provide a theoretical understanding of how the degree of polymerization affects the binding avidity of multivalent polymers. We show that longer polymers increase binding avidity to multivalent targets but reach a limit in binding avidity at high degrees of polymerization. We also show that when interacting with multiple targets simultaneously, longer polymers are able to use intertarget interactions to promote clustering and improve binding efficiency. We expect our results to narrow the design space for optimizing the structure and effectiveness of multivalent inhibitors as well as be useful to understand biological design strategies for multivalent binding.

PMID: 31400918 [PubMed - as supplied by publisher]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/08/11

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"systems biology"

These pubmed results were generated on 2019/08/10

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"systems biology"

These pubmed results were generated on 2019/08/09

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