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Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...

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A Multilayer Microfluidic Platform for the Conduction of Prolonged Cell-Free Gene Expression
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Evolving modular genetic regulatory networks with a recursive, top-down approach.

Javier Garcia-Bernardo1, Margaret J Eppstein1

  • 1Department of Computer Science, University of Vermont, Burlington, VT 05405 USA.

Systems and Synthetic Biology
|April 11, 2017
PubMed
Summary

This study introduces a novel top-down method for designing minimal genetic regulatory networks (GRNs) for synthetic biology. The approach efficiently evolves complex GRNs by starting dense and then pruning, enabling precise cellular function control.

Keywords:
Differential evolutionGenetic network inferenceGenetic regulatory networksSynthetic biology

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Area of Science:

  • Synthetic Biology
  • Computational Biology
  • Systems Biology

Background:

  • Designing genetic regulatory networks (GRNs) for specific cellular functions is a key goal in synthetic biology.
  • Identifying minimal GRNs that exhibit desired time-series behaviors remains a significant challenge.

Purpose of the Study:

  • To develop a 'top-down' computational approach for evolving minimal genetic regulatory networks (GRNs).
  • To demonstrate the recursive bootstrapping of larger, modular GRNs from smaller evolved networks.

Main Methods:

  • Utilized differential evolution (DE) to evolve interaction coefficients in dense GRNs.
  • Implemented an aggressive pruning strategy to remove excess interactions once target behaviors were identified.
  • Incorporated a penalty term to encourage network minimality.

Main Results:

  • Successfully rediscovered known small GRNs for toggle switch and oscillatory circuits.
  • Evolved complex, modular GRNs by using previously identified GRNs as non-evolvable subnetworks.
  • The proposed method, with aggressive pruning and penalty terms, identified minimal or near-minimal GRNs, unlike canonical DE methods.

Conclusions:

  • The 'top-down' DE approach with pruning is effective for evolving minimal genetic regulatory networks (GRNs).
  • This method facilitates the design of complex, modular biological systems for synthetic biology applications.