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Related Concept Videos

Repressible Operon: trp Operon01:21

Repressible Operon: trp Operon

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The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
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Inducible Operons: lac Operon01:25

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The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA...
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Operon Model01:23

Operon Model

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The operon model represents a fundamental mechanism of gene regulation in prokaryotes, enabling coordinated expression of genes involved in related metabolic or functional pathways. Operons consist of structural genes, a promoter, and an operator, with transcription regulated by repressors, activators, and small effector molecules.Structure and Function of OperonsAn operon is a cluster of structural genes transcribed together under the control of a single promoter. The promoter region...
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Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

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Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
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Operons02:09

Operons

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Prokaryotes can control gene expression through operons—DNA sequences consisting of regulatory elements and clustered, functionally related protein-coding genes. Operons use a single promoter sequence to initiate transcription of a gene cluster (i.e., a group of structural genes) into a single mRNA molecule. The terminator sequence ends transcription. An operator sequence, located between the promoter and structural genes, prohibits the operon’s transcriptional activity if bound by...
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Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

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The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
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Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
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An Orthogonal Permease-Inducer-Repressor Feedback Loop Shows Bistability.

Robert Gnügge1,2, Lekshmi Dharmarajan2, Moritz Lang2

  • 1Life Science Zurich Ph.D. Program on Molecular and Translational Biomedicine, and Competence Centre for Personalized Medicine, ETH Zurich , 8093 Zurich, Switzerland.

ACS Synthetic Biology
|May 6, 2016
PubMed
Summary
This summary is machine-generated.

Synthetic biology engineered a feedback loop system in yeast to understand biological switches. This minimal circuit replicates natural systems, showing that a single feedback loop can explain complex behaviors in metabolic gene regulation.

Keywords:
S. cerevisiaebistabilitygenetic circuithysteresisswitchsynthetic biology

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Area of Science:

  • Synthetic biology
  • Systems biology
  • Molecular biology

Background:

  • Biological feedback loops are crucial for cellular functions like differentiation and signal transduction robustness.
  • Natural feedback loops are often complex, making it difficult to pinpoint key regulatory components.
  • Minimal synthetic systems offer a way to dissect the essential mechanisms driving biological behaviors.

Purpose of the Study:

  • To engineer a synthetic permease-inducer-repressor circuit in Saccharomyces cerevisiae.
  • To investigate if a transport-mediated positive feedback loop is a core mechanism for switch-like behavior in metabolic gene networks.
  • To compare the synthetic system's behavior with natural systems like the GAL and lac operons.

Main Methods:

  • Engineering a synthetic permease-inducer-repressor system in yeast.
  • Characterizing the synthetic circuit using deterministic and stochastic mathematical modeling.
  • Analyzing bistability and hysteresis in the engineered system.

Main Results:

  • The synthetic system exhibited bistable and hysteretic behavior, mirroring natural metabolic gene networks.
  • The range of inducer concentration for bistability and switching rates were dependent on repressor concentration.
  • A single feedback loop in the permease-inducer-repressor circuit was sufficient to explain observed bistability.

Conclusions:

  • A simple, transport-mediated positive feedback loop can be a fundamental mechanism for switch-like regulation in metabolic gene networks.
  • The synthetic biology approach of recreating natural systems with orthogonal parts is valuable for identifying crucial network components.
  • This methodology can be extended to study other biological systems, including signaling pathways.