Small Molecule Screening in Zebrafish

Peal, David S.; Peterson, Randall T.; Milan, David J.

doi:10.1007/s12265-010-9212-8

Cited by 51 publications

(36 citation statements)

References 39 publications

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“…Clearly, zebrafish also provides an inexpensive whole-animal vertebrate model for screening a library of small molecules, cell-or tissue receptorspecific compounds against viral pathogens or anti-angiogenic or anti-inflammatory compounds. 24,[46][47][48][49] One study has already employed this model to confirm the antiviral effect of acyclovir using HSV-1 infected zebrafish. 21 Ideally, zebrafish in a 96-well format can be treated with antibodies 50 or compounds targeting specific cells/tissues or modified antiviral peptides with an objective to have higher efficacy.…”

Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning

confidence: 99%

Zebrafish: Modeling for Herpes Simplex Virus Infections

et al. 2014

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For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

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Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning

confidence: 99%

Zebrafish: Modeling for Herpes Simplex Virus Infections

et al. 2014

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“…One method to help determine the molecular effects of identified compounds is to select a drug library of known bioactives for screening, where mechanisms can be potentially deduced from previously annotated data. Additionally, chemoinformatic algorithms, like Discovery gate, are available for use that can compare structural similarities of a compound against a database of compounds with ascribed mechanisms 14 . Yet another way to elucidate the mechanism of a compound would be to generate a microarray profile after treatment and then query this profile in a compilation of microarray drug profiles, such as Connectivity Map, searching for mechanistically defined compounds that elicit a similar effect 14 .…”

Section: Discussionmentioning

confidence: 99%

“…To date, a myriad of chemical genetic screens have been performed using zebrafish embryos in particular, as compound delivery can be accomplished by immersing embryos in media containing the drug of interest [12][13][14][15] . Further, there have been numerous scientific and technological advances to make chemical genetic screens possible and manageable [16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos

Poureetezadi

Donahue

Wingert

2014

JoVE

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Zebrafish have become a widely used model organism to investigate the mechanisms that underlie developmental biology and to study human disease pathology due to their considerable degree of genetic conservation with humans. Chemical genetics entails testing the effect that small molecules have on a biological process and is becoming a popular translational research method to identify therapeutic compounds. Zebrafish are specifically appealing to use for chemical genetics because of their ability to produce large clutches of transparent embryos, which are externally fertilized. Furthermore, zebrafish embryos can be easily drug treated by the simple addition of a compound to the embryo media. Using whole-mount in situ hybridization (WISH), mRNA expression can be clearly visualized within zebrafish embryos. Together, using chemical genetics and WISH, the zebrafish becomes a potent whole organism context in which to determine the cellular and physiological effects of small molecules. Innovative advances have been made in technologies that utilize machine-based screening procedures, however for many labs such options are not accessible or remain cost-prohibitive. The protocol described here explains how to execute a manual high-throughput chemical genetic screen that requires basic resources and can be accomplished by a single individual or small team in an efficient period of time. Thus, this protocol provides a feasible strategy that can be implemented by research groups to perform chemical genetics in zebrafish, which can be useful for gaining fundamental insights into developmental processes, disease mechanisms, and to identify novel compounds and signaling pathways that have medically relevant applications.

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“…Other efforts have utilized functional screens to discover small molecules that would suppress the long-QT phenotype irrespective of mechanism. An interesting approach has been reported using the breakdance (see section 4.3) mutant to screen for molecules that would rescue the phenotype (Peal et al, 2010). The investigators isolated 2 compounds that shortened the APD.…”

Section: Exploring Novel Therapeutic Modalitiesmentioning

confidence: 99%