Phenotypic Drug Screening
Phenotypic Drug Screening - Related Videos
09:40
RNAi Screening to Identify Postembryonic Phenotypes in C. elegans
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Cited by 9 •
2012
We describe a sensitized method to identify postembryonic regulators of protein expression and localization in C. elegans using an RNAi-based genomic screen and an integrated transgene that expresses a functional, fluorescently tagged protein.
14:51
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
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Cited by 2 •
2022
High-throughput RNA interference (RNAi) screening using a pool of lentiviral shRNAs can be a tool to detect therapeutically relevant synthetic lethal targets in malignancies. We provide a pooled shRNA screening approach to investigate the epigenetic effectors in acute myeloid leukemia (AML).
15:28
A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
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Cited by 30 •
2014
Here, we describe a phenotypic assay applicable to the High-throughput/High-content screens of small-interfering synthetic RNA (siRNA), chemical compound, and Mycobacterium tuberculosis mutant libraries. This method relies on the detection of fluorescently labeled Mycobacterium tuberculosis within fluorescently labeled host cell using automated confocal microscopy.
08:50
Genetic Screens
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2023
Genetic screens are critical tools for defining gene function and understanding gene interactions. Screens typically involve mutating genes and then assessing the affected organisms for phenotypes of interest. The process can be “forward”, where mutations are generated randomly to identify unknown genes responsible for the phenotypes, or it can be “reverse”, where specific genes are targeted for mutation to observe what phenotypes are produced.Here, JoVE reviews various types of genetic...
11:28
3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug Screening
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Cited by 7 •
2017
This protocol describes the fabrication of elastic 3D macroporous microcryogels by integrating microfabrication with cryogelation technology. Upon loading with cells, 3D microtissues are generated, which can be readily injected in vivo to facilitate regenerative therapy or assembled into arrays for in vitro high-throughput drug screening.
FAQs
The choice of disease-relevant model strongly shapes what phenotypic drug screening can reveal. Cells, tissues, or organisms may expose different effects on pathogen growth, host-cell activation, or inflammatory responses. Matching the model and measurable readout to the biological question helps connect compound activity with a meaningful disease-related outcome.
Phenotypic drug screening begins with an observable biological effect instead of requiring a predefined molecular target. This strategy can identify compounds that influence several components of a disease process or reveal unexpected mechanisms. Subsequent studies must determine the molecular targets and mechanisms of action, creating a path from observed activity to mechanistic understanding.
Different readouts capture different biological consequences of compound exposure. Automated imaging, viability measurements, and reporter signals can monitor pathogen growth, host-cell activation, or inflammatory responses. Considering the selected signal alongside the disease model helps distinguish relevant activity from a narrow measurement and can expose effects on host-pathogen interactions or immune pathways.
A typical workflow tests candidate molecules in cells, tissues, or organisms that reflect the disease context, then records measurable responses with an appropriate assay or readout. Active compounds are identified from changes such as altered pathogen growth or immune activity. Follow-up studies then investigate molecular targets, mechanisms of action, and safety profiles.
The approach is useful when disease behavior depends on interactions among pathogens, host cells, and immune pathways rather than on one established target. Testing compounds in relevant biological models can uncover therapeutic opportunities that affect pathogen growth, host-cell activation, or inflammatory responses. It therefore supports investigation of both pathogen-directed and host-associated effects.
An active compound provides a starting point for more than simple activity ranking. Follow-up analysis can identify its molecular target and mechanism of action, while safety studies assess whether the response is suitable for continued development. These findings guide lead optimization and help determine whether the compound has translational potential in immunology or infection research.