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Related Concept Videos

Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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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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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...

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DNA-affinity-purified Chip (DAP-chip) Method to Determine Gene Targets for Bacterial Two component Regulatory Systems
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CDA: combinatorial drug discovery using transcriptional response modules.

Ji-Hyun Lee1, Dae Gyu Kim, Tae Jeong Bae

  • 1Medicinal Bioconvergence Research Center, Seoul National University, Seoul, South Korea.

Plos One
|August 21, 2012
PubMed
Summary
This summary is machine-generated.

This study introduces Combinatorial Drug Assembler (CDA), a system for discovering synergistic drug combinations to improve cancer therapy. CDA identifies effective multi-drug treatments by analyzing gene expression, showing promise for lung and breast cancer.

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Area of Science:

  • Genomics and Bioinformatics
  • Cancer Therapeutics
  • Systems Biology

Background:

  • Single-target anticancer therapies are often ineffective due to pathway crosstalk.
  • Multi-component therapies offer potential for increased efficacy and reduced toxicity.
  • Combinatorial drug discovery is gaining traction due to its potential to overcome drug resistance.

Purpose of the Study:

  • To develop a genomics and bioinformatics system, Combinatorial Drug Assembler (CDA), for identifying synergistic drug combinations.
  • To target multiple signaling pathways simultaneously for enhanced cancer treatment.
  • To provide a rational approach for combinatorial drug discovery.

Main Methods:

  • Gene expression profiling to analyze signaling pathway components.
  • Expression pattern matching to compare cell line data with drug-treated profiles.
  • Identification of overlapping gene expression patterns to predict effective drug pairs for combination therapy.

Main Results:

  • In vitro validation on non-small cell lung cancer and triple-negative breast cancer cells.
  • Discovery of two synergistic drug pairs for lung cancer treatment.
  • Identification of synergistic effects of halofantrine and vinblastine on triple-negative breast cancer cells.

Conclusions:

  • CDA offers a novel method for rational drug combination discovery.
  • CDA, integrated with phExplorer, provides functional insights into drug combinations.
  • The CDA system is publicly accessible for research use.