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Related Concept Videos

Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow
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Engineered TAL Effector modulators for the large-scale gain-of-function screening.

Hanshuo Zhang1, Juan Li2, Sha Hou3

  • 1Biomedical Engineering Department, College of Engineering, Peking University Yan Nan Yuan 60, Beijing 100871, China.

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Summary

Researchers developed novel TALE modulators for gene function studies. Key factors for TALE transcription activity in vivo include chromatin accessibility and proximity to the transcription start site.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Synthetic Biology

Background:

  • TALE (Tale Effector) proteins are engineered DNA-binding proteins with applications in gene regulation.
  • Designing effective TALE modulators is challenging due to incomplete understanding of TALE-DNA interactions.

Purpose of the Study:

  • To design and synthesize novel TALE modulators.
  • To identify key factors influencing TALE transcription activity in vivo.
  • To demonstrate the utility of TALE modulators in functional genomics screens.

Main Methods:

  • Synthesis of over 200 TALE modulators.
  • In vivo assessment of TALE transcription activity.
  • Gain-of-function screening in four cell lines using migration/invasion assays.

Main Results:

  • Identified chromatin accessibility and distance from the transcription start site as critical factors for TALE activity.
  • Successfully implemented TALE modulators in gain-of-function screens for cellular behavior analysis.
  • Developed a novel TALE-TALE modulator for transcriptional inhibition of target genes.

Conclusions:

  • TALE modulators show significant potential for gene function studies.
  • These modulators can be used to reprogram cellular behaviors.
  • Findings support the application of TALE modulators in clinical investigations.