Services

Here at flow, we provide various research services for academic collaborators and private partners. Our services include research studies, drug screening, development of new reporter lines, zebrafish embryos and adults, and training in zebrafish husbandry, research and molecular approaches. 

Advantages of using larval zebrafish for drug discovery:

  • Zebrafish are inexpensive and easy to produce in large quantity

  • Zebrafish have a genome with 70% homology to humans

  • Gene editing can be easily done in first generation embryos

  • Drug exposure is done by adding drugs to fish water 

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Phenotype-based drug discovery in larval zebrafish

  • Phenotype-based drug screening of chemical libraries (FDA-approved, drug repurposing libraries). Our drug screening platform allows fast screening of drug candidates in larval zebrafish. We assess phenotypes such as behaviors in live fish and biomarkers in reporter lines.  Our platform combines bioimager with 48 and 96 well plates, and behavioral assessment systems.

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Disease models

Our drug discovery platform focuses on neurological and cardiovascular diseases:

  • Seizure/Epilepsy assays. Behavioral assessments in zebrafish models of epilepsy (gabra1-/-) or PTZ exposure.

  • Nociception assays. Behavioral response to nociceptive stimuli (formalin, AITC, heat).

  • Respiratory assays. Changes in respiratory behaviors (respiratory depression) in response to drug exposure.

  • Zebrafish models of Parkinson's Disease:

 - Neurotoxicant zebrafish models of PD. Loss of dopamine neurons using 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) or MPP+ combined with locomotor assessment in larval zebrafish.

 - Loss of dopamine neurons with MPTP combined with the reporter line for dopamine transporter dat Tg(dat:EGFP) also called Tg(slc6a3:EGFP)9. 
- Knockdown of genes involved in Parkinson’s Diseases in larval zebrafish.
- Transient knockdowns of PD-associated genes (Dj-1, pink1, and Parkin) using morpholino antisense oligonucleotides and locomotor assessments.

  • Zebrafish models of cardiovascular diseases. Vascular endothelial growth factor receptor kdr-like (kdrl-GFP) reporter line. 

Drug safety profile

  • Mortality assay. Survival rate dose-response. Drug concentration for 50% mortality rate (LC50). Drug treatment for 48-72h in 3-5 days post-fertilization larvae.

  • Neurotoxicity. Seizure liability assay, locomotor assay. Seizure-like swimming behaviors.

  • Cardiotoxicity assay. Heat rate, arrhythmia, cardiac arrest. Cardiotoxicity using kdrl-GFP (previously called flk-GFP) line.

  • Hepatotoxicity assay. Drug-induced liver injury. Quantification of liver size and yolk sac retention.

Gene editing in zebrafish

  • Targeted mutagenesis of genes of interest using CRISPR/Cas9 technology. Rapid and robust biallelic mutations performed in microinjected single-cell embryos allowing phenotype-driven mutagenesis screens or permanent mutants. Using CRISPR/Cas9, we can knockout a gene of interest on day 1 of fertilization and perform behavioral profiling the following week. 

  • Transient knockdown using morpholino antisense oligonucleotides. Short-term knockdown in gene expression up to 4 days post-fertilization.

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Need more details? Contact us

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