TAS::75 0862::TAS R&D-OTHER R & D-B RES

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There is a need for highly predictive toxicological assays that can be performed at moderate to high throughput and that reduce reliance on mammalian models. While biochemical and cell-based assays provide high-throughput they do not provide the sensitivity to the broad range of developmental and physiological effects that whole animal testing can provide. Zebrafish-based toxicology assays may represent a middle ground that permits greatly reduced reliance on mammals and other adult vertebrate model organisms while retaining many advantages of those systems. The overall technical objective is to develop an automated Doppler-OCT based imaging system for toxicological studies using zebrafish models. Those assays will identify developmental and cardiac toxins by measuring morphological characteristics such as length, degree of curvature and other deviations from normal zebrafish embryonic proportions, as well as physiological characteristics such as heart rate, rhythm, and cardiac output. We anticipate that preliminary data generated during the Phase I program will demonstrate the feasibility of the zebrafish as a toxicological model and will demonstrate the ability of the imaging system to measure key parameters correlated with toxicity.