scholarly journals The Applications of Promoter-gene-Engineered Biosensors

Sensors ◽  
2018 ◽  
Vol 18 (9) ◽  
pp. 2823 ◽  
Author(s):  
Yingzhu Feng ◽  
Zhangzhang Xie ◽  
Xuanlong Jiang ◽  
Zhen Li ◽  
Yuping Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
High Throughput Screening ◽  
Large Scale ◽  
Value Added ◽  
Site Directed Mutagenesis ◽  
Biomedical Science ◽  
Genetic Circuit ◽  
Genomic Libraries ◽  
Promoter Gene

A promoter is a small region of a DNA sequence that responds to various transcription factors, which initiates a particular gene expression. The promoter-engineered biosensor can activate or repress gene expression through a transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids, or a redox molecule; however, there are few reported applications of promoter-enhanced biosensors. This review paper highlights the strategies of construction of promoter gene-engineered biosensors with human and bacteria genetic promoter arrays with regard to high-throughput screening (HTS) molecular drugs, the study of the membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factors, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These biosensors’ sensitivity and specificity can be further improved by the proposed approaches of Mn2+ and Mg2+ added random error-prone PCR that is a technique used to generate randomized genomic libraries and site-directed mutagenesis approach, which is applied for the construction of bacteria’s “mutant library”. This is expected to establish a flexible HTS platform (biosensor array) to large-scale screen transcription factor-acting drugs, reduce the toxicity of intermediate compounds, and construct a gene-dynamic regulatory system in “push and pull” mode, in order to effectively regulate the valuable medicinal product production. These proposed novel promoter-engineered biosensors aiding in synthetic genetic circuit construction will maximize the efficiency of the bio-synthesis of medicinal compounds, which will greatly promote the development of microbial metabolic engineering and biomedical science.

scholarly journals The Applications of Promoter-Gene Engineered Bio-Sensors

2018 ◽  
Author(s):  
Yingzhu Feng ◽  
Zhangzhang Xie ◽  
Xuanlong Jiang ◽  
Zhen Li ◽  
Yuping Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
High Throughput Screening ◽  
Large Scale ◽  
Regulatory System ◽  
Value Added ◽  
Site Directed Mutagenesis ◽  
Biomedical Science ◽  
Genetic Circuit ◽  
Promoter Gene

Promoter is a small region of DNA sequence in response to various transcription factors, which initiates a particular gene expression. The promoter-engineered bio-sensor can activate or repress gene expression through transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids or redox molecule, however, the reported applications of promoter enhanced bio-sensor are not too much. This review paper highlights the strategies of construction of promoter-gene engineered bio-sensor with human and bacteria’s genetic promoter array for high-throughput screening (HTS) molecular drugs, study of membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factor, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These bio-sensors’s sensitivity and specificity can be further improved by proposed approaches of Mn2+ and Mg2+ added random Error-prone PCR and site-directed mutagenesis which is applied for construction of bacteria’s “mutant library”. It is expected to establish flexible HTS platform (Bio-sensor array) to large-scale screen transcription factor-acting drugs, reducing the toxicity of intermediate compounds, and constructing gene dynamic regulatory system in “push and pull” mode to effectively regulate the valuable medicinal product production. This proposed novel promoter-engineered biosensors aided synthetic genetic circuit construction will maximize the efficiency of bio-synthesis of medicinal compound, which will greatly promote the development of microbial metabolic engineering and biomedical science.

scholarly journals Altered Regulation of 15-Acetyldeoxynivalenol Production in Fusarium graminearum

2000 ◽  
Vol 66 (5) ◽  
pp. 2062-2065 ◽  
Author(s):  
Lifeng Chen ◽  
Susan P. McCormick ◽  
Thomas M. Hohn
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Reporter Gene ◽  
Fusarium Graminearum ◽  
Large Scale ◽  
Fold Increase ◽  
Gene Clusters ◽  
Gus Expression ◽  
Plasmid Integration ◽  
Pathway Gene

ABSTRACT Most Fusarium graminearum isolates produce low or undetectable levels of trichothecenes in liquid shake cultures, making it difficult to perform biochemical studies of trichothecene biosynthesis. To develop strains with higher levels of trichothecene production under liquid shake conditions we transformed F. graminearum with both a reporter gene containing a homologous trichothecene pathway gene promoter (TRI5) and a gene encoding a heterologous trichothecene pathway transcription factor (TRI6). The TRI5 and TRI6 genes are part of the trichothecene pathway gene clusters of both Fusarium sporotrichioides and F. graminearum. These genes encode trichodiene synthase (encoded by TRI5), the first enzyme in the trichothecene pathway, and a transcription factor (encoded by TRI6) required for pathway gene expression. Transformation of F. graminearum with plasmids containing either an F. graminearum TRI5 promoter fragment (FGTRI5P ) or FGTRI5P coupled with the β-d-glucuronidase (GUS) reporter gene resulted in the identification of several transformants capable of producing 45 to 200 mg of 15-acetyldeoxynivalenol (15-ADON)/liter in liquid shake culture after 7 days. Increased 15-ADON production was only observed in transformants where plasmid integration occurred through the FGTRI5P sequence and was not accompanied by increased GUS expression. 15-ADON production was further increased in liquid culture up to 1,200 mg/liter following introduction of the F. sporotrichioides TRI6 gene (FSTRI16) into F. graminearum. The effects of FSTRI6 on 15-ADON production also depended on plasmid integration via homologous recombination of the FGTRI5P fragment and resulted in a 100-fold increase in GUS expression. High-level production of 15-ADON in liquid shake cultures provides a convenient method for large-scale trichothecene preparation. The results suggest that targeting transformation vector integration toFGTRI5P alters pathway gene expression and are consistent with the proposed conservation of TRI6 function betweenFusarium species.

scholarly journals Multiple transcription factors co-regulate the Mycobacterium tuberculosis adaptation response to vitamin C

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Malobi Nandi ◽  
Kriti Sikri ◽  
Neha Chaudhary ◽  
Shekhar Chintamani Mande ◽  
Ravi Datta Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Mycobacterium Tuberculosis ◽  
Vitamin C ◽  
Large Scale ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Transcriptional Regulators ◽  
Transcriptional Regulatory ◽  
Modulation Of Gene Expression

Abstract Background Latent tuberculosis infection is attributed in part to the existence of Mycobacterium tuberculosis in a persistent non-replicating dormant state that is associated with tolerance to host defence mechanisms and antibiotics. We have recently reported that vitamin C treatment of M. tuberculosis triggers the rapid development of bacterial dormancy. Temporal genome-wide transcriptome analysis has revealed that vitamin C-induced dormancy is associated with a large-scale modulation of gene expression in M. tuberculosis. Results An updated transcriptional regulatory network of M.tuberculosis (Mtb-TRN) consisting of 178 regulators and 3432 target genes was constructed. The temporal transcriptome data generated in response to vitamin C was overlaid on the Mtb-TRN (vitamin C Mtb-TRN) to derive insights into the transcriptional regulatory features in vitamin C-adapted bacteria. Statistical analysis using Fisher’s exact test predicted that 56 regulators play a central role in modulating genes which are involved in growth, respiration, metabolism and repair functions. Rv0348, DevR, MprA and RegX3 participate in a core temporal regulatory response during 0.25 h to 8 h of vitamin C treatment. Temporal network analysis further revealed Rv0348 to be the most prominent hub regulator with maximum interactions in the vitamin C Mtb-TRN. Experimental analysis revealed that Rv0348 and DevR proteins interact with each other, and this interaction results in an enhanced binding of DevR to its target promoter. These findings, together with the enhanced expression of devR and Rv0348 transcriptional regulators, indicate a second-level regulation of target genes through transcription factor- transcription factor interactions. Conclusions Temporal regulatory analysis of the vitamin C Mtb-TRN revealed that there is involvement of multiple regulators during bacterial adaptation to dormancy. Our findings suggest that Rv0348 is a prominent hub regulator in the vitamin C model and large-scale modulation of gene expression is achieved through interactions of Rv0348 with other transcriptional regulators.

scholarly journals Comparison of the theoretical and real-world evolutionary potential of a genetic circuit.

2014 ◽  
Author(s):  
Manuel Razo-Mejia ◽  
James Boedicker ◽  
Daniel Jones ◽  
Alexander de Luna ◽  
Justin Block Kinney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Large Scale ◽  
Point Mutations ◽  
Promoter Sequence ◽  
Binding Energies ◽  
Genetic Circuit ◽  
Lac Operon ◽  
Evolutionary Potential ◽  
Operon Regulation

With the development of next-generation sequencing technologies, many large scale experimental efforts aim to map genotypic variability among individuals. This natural variability in populations fuels many fundamental biological processes, ranging from evolutionary adaptation and speciation to the spread of genetic diseases and drug resistance. An interesting and important component of this variability is present within the regulatory regions of genes. As these regions evolve, accumulated mutations lead to modulation of gene expression, which may have consequences for the phenotype. A simple model system where the link between genetic variability, gene regulation and function can be studied in detail is missing. In this article we develop a model to explore how the sequence of the wild-type lac promoter dictates the fold change in gene expression. The model combines single-base pair resolution maps of transcription factor and RNA polymerase binding energies with a comprehensive thermodynamic model of gene regulation. The model was validated by predicting and then measuring the variability of lac operon regulation in a collection of natural isolates. We then implement the model to analyze the sensitivity of the promoter sequence to the regulatory output, and predict the potential for regulation to evolve due to point mutations in the promoter region.

Accelerated Discovery of High-Refractive-Index Polyimides via First-Principles Molecular Modeling, Virtual High-Throughput Screening, and Data Mining

2019 ◽  
Author(s):  
Mohammad Atif Faiz Afzal ◽  
Mojtaba Haghighatlari ◽  
Sai Prasad Ganesh ◽  
Chong Cheng ◽  
Johannes Hachmann
Keyword(s):  
Data Mining ◽  
Refractive Index ◽  
High Throughput ◽  
First Principles ◽  
High Throughput Screening ◽  
Large Scale ◽  
Computational Study ◽  
High Refractive Index ◽  
Structural Features ◽  
Learning Program

<div>We present a high-throughput computational study to identify novel polyimides (PIs) with exceptional refractive index (RI) values for use as optic or optoelectronic materials. Our study utilizes an RI prediction protocol based on a combination of first-principles and data modeling developed in previous work, which we employ on a large-scale PI candidate library generated with the ChemLG code. We deploy the virtual screening software ChemHTPS to automate the assessment of this extensive pool of PI structures in order to determine the performance potential of each candidate. This rapid and efficient approach yields a number of highly promising leads compounds. Using the data mining and machine learning program package ChemML, we analyze the top candidates with respect to prevalent structural features and feature combinations that distinguish them from less promising ones. In particular, we explore the utility of various strategies that introduce highly polarizable moieties into the PI backbone to increase its RI yield. The derived insights provide a foundation for rational and targeted design that goes beyond traditional trial-and-error searches.</div>

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Exposure Assessment ◽  
Large Scale ◽  
First Generation ◽  
Cancer Epidemiology ◽  
Policy Changes ◽  
The Past ◽  
New Generation

The purpose of this review is to evaluate progress inmolecular epidemiology over the past 24 years in canceretiology and prevention to draw lessons for futureresearch incorporating the new generation of biomarkers.Molecular epidemiology was introduced inthe study of cancer in the early 1980s, with theexpectation that it would help overcome some majorlimitations of epidemiology and facilitate cancerprevention. The expectation was that biomarkerswould improve exposure assessment, document earlychanges preceding disease, and identify subgroupsin the population with greater susceptibility to cancer,thereby increasing the ability of epidemiologic studiesto identify causes and elucidate mechanisms incarcinogenesis. The first generation of biomarkers hasindeed contributed to our understanding of riskandsusceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes havebeen mounted to reduce riskfrom several importantenvironmental carcinogens. Several new and promisingbiomarkers are now becoming available for epidemiologicstudies, thanks to the development of highthroughputtechnologies and theoretical advances inbiology. These include toxicogenomics, alterations ingene methylation and gene expression, proteomics, andmetabonomics, which allow large-scale studies, includingdiscovery-oriented as well as hypothesis-testinginvestigations. However, most of these newer biomarkershave not been adequately validated, and theirrole in the causal paradigm is not clear. There is a needfor their systematic validation using principles andcriteria established over the past several decades inmolecular cancer epidemiology.

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