A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay

Douglas W. Todd, Rohit C. Philip, Maki Niihori, Ryan A. Ringle, Kelsey R. Coyle, Sobia F. Zehri, Leanne Zabala, Jordan A. Mudery, Ross H. Francis, Jeffrey J. Rodriguez, Abraham Jacob

Research output: Research - peer-reviewArticle

Abstract

Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

LanguageEnglish (US)
Pages331-342
Number of pages12
JournalZebrafish
Volume14
Issue number4
DOIs
StatePublished - Aug 1 2017

Fingerprint

Danio rerio
hairs
assays
cells
Zebrafish
dosage
cisplatin
image analysis
drugs
testing
methodology
Cisplatin
Pharmaceutical Preparations
microcomputers
raspberries
hearing
water flow
ears
biomarkers
bioassays

Keywords

  • behavioral assay
  • drug discovery and development
  • hearing and hearing loss
  • ototoxicity
  • rheotaxis
  • zebrafish

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Developmental Biology

Cite this

Todd, D. W., Philip, R. C., Niihori, M., Ringle, R. A., Coyle, K. R., Zehri, S. F., ... Jacob, A. (2017). A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay. Zebrafish, 14(4), 331-342. DOI: 10.1089/zeb.2016.1412

A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay. / Todd, Douglas W.; Philip, Rohit C.; Niihori, Maki; Ringle, Ryan A.; Coyle, Kelsey R.; Zehri, Sobia F.; Zabala, Leanne; Mudery, Jordan A.; Francis, Ross H.; Rodriguez, Jeffrey J.; Jacob, Abraham.

In: Zebrafish, Vol. 14, No. 4, 01.08.2017, p. 331-342.

Research output: Research - peer-reviewArticle

Todd, DW, Philip, RC, Niihori, M, Ringle, RA, Coyle, KR, Zehri, SF, Zabala, L, Mudery, JA, Francis, RH, Rodriguez, JJ & Jacob, A 2017, 'A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay' Zebrafish, vol 14, no. 4, pp. 331-342. DOI: 10.1089/zeb.2016.1412
Todd DW, Philip RC, Niihori M, Ringle RA, Coyle KR, Zehri SF et al. A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay. Zebrafish. 2017 Aug 1;14(4):331-342. Available from, DOI: 10.1089/zeb.2016.1412
Todd, Douglas W. ; Philip, Rohit C. ; Niihori, Maki ; Ringle, Ryan A. ; Coyle, Kelsey R. ; Zehri, Sobia F. ; Zabala, Leanne ; Mudery, Jordan A. ; Francis, Ross H. ; Rodriguez, Jeffrey J. ; Jacob, Abraham. / A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay. In: Zebrafish. 2017 ; Vol. 14, No. 4. pp. 331-342
@article{97f05d0b0b46479e9f230102ae58390b,
title = "A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay",
abstract = "Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.",
keywords = "behavioral assay, drug discovery and development, hearing and hearing loss, ototoxicity, rheotaxis, zebrafish",
author = "Todd, {Douglas W.} and Philip, {Rohit C.} and Maki Niihori and Ringle, {Ryan A.} and Coyle, {Kelsey R.} and Zehri, {Sobia F.} and Leanne Zabala and Mudery, {Jordan A.} and Francis, {Ross H.} and Rodriguez, {Jeffrey J.} and Abraham Jacob",
year = "2017",
month = "8",
doi = "10.1089/zeb.2016.1412",
volume = "14",
pages = "331--342",
journal = "Zebrafish",
issn = "1545-8547",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay

AU - Todd,Douglas W.

AU - Philip,Rohit C.

AU - Niihori,Maki

AU - Ringle,Ryan A.

AU - Coyle,Kelsey R.

AU - Zehri,Sobia F.

AU - Zabala,Leanne

AU - Mudery,Jordan A.

AU - Francis,Ross H.

AU - Rodriguez,Jeffrey J.

AU - Jacob,Abraham

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

AB - Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

KW - behavioral assay

KW - drug discovery and development

KW - hearing and hearing loss

KW - ototoxicity

KW - rheotaxis

KW - zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85024389464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024389464&partnerID=8YFLogxK

U2 - 10.1089/zeb.2016.1412

DO - 10.1089/zeb.2016.1412

M3 - Article

VL - 14

SP - 331

EP - 342

JO - Zebrafish

T2 - Zebrafish

JF - Zebrafish

SN - 1545-8547

IS - 4

ER -