CDS&E: Modeling the Zebrafish Model Organism Toward Reducing, Refining, and Replacing Animal Experiments

CDS

• 批准号: 1505832
• 负责人: Maurizio Porfiri
• 金额: $ 32.5万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1505832&HistoricalAwards=false
• 关键词: CDS& Modeling; Zebrafish; Model; Organism

Zebrafish are gaining momentum as laboratory species for the investigation of several functional and dysfunctional biological processes in humans, including the fundamental mechanisms modulating emotional patterns, learning processes, and individual and social response to alcohol and drugs of abuse. However, as with rodents and primates, experimentation with zebrafish constitutes a complicated and contemporary ethical issue that demands the exploration of alternative testing methods to reduce the number of subjects, refine the experimental designs with animal welfare in mind, and possibly replace live animals with other scientific instruments. This award supports fundamental research in computational and data-enabled science and engineering to aid the design of unprecedented "in silico" studies on zebrafish behavior. An experimentally-validated computational platform will be established to help decrease the number of animal subjects needed for experiments, quantify variables of interest in animal behavior without increasing animal discomfort, and perform pilot trials preceding animal experiments. All of these factors will contribute to a reduction in animal use and suffering. Interdisciplinary formal and informal education activities will complement the research and will provide opportunities to underprivileged students within economically-disadvantaged Brooklyn communities.This research program seeks to advance computational modeling of animal behavior towards improving animal welfare in preclinical research. Specifically, this award will establish a computational modeling framework of zebrafish behavior, through experimentally-informed modeling choices, model calibration via rigorous statistical techniques, and, ultimately, experimental validation against new experiments. The framework will be based on stochastic differential equations to enable the prediction of zebrafish locomotion in two and three dimensions, in larvae and adults, with a single individual and in groups, in the presence of external stimuli, and under the effect of psychoactive compounds. This novel computational tool will be used to assess the feasibility of: performing a priori power analysis on the basis of simulated data, selecting explanatory variables, analyzing the reproducibility in the face of biological confounds, and inferring experimental outcomes without the need for experiments. While the study will primarily rely on available experimental data, additional experiments will be conducted to dissect salient behavioral cues and demonstrate the potential of in silico experimentation.

斑马鱼作为实验室物种，在研究人类多种功能性和功能失调的生物过程方面正在获得动力，包括调节情绪模式、学习过程以及个人和社会对酒精和滥用药物的反应的基本机制。然而，与啮齿动物和灵长类动物一样，斑马鱼实验构成了一个复杂的当代伦理问题，需要探索替代测试方法以减少受试者数量，在考虑动物福利的情况下完善实验设计，并可能用其他动物代替活体动物。科学仪器。该奖项支持计算和数据驱动的科学与工程方面的基础研究，以帮助设计有关斑马鱼行为的前所未有的“计算机”研究。将建立一个经过实验验证的计算平台，以帮助减少实验所需的动物受试者数量，在不增加动物不适的情况下量化动物行为中感兴趣的变量，并在动物实验之前进行试点试验。所有这些因素都将有助于减少动物的使用和痛苦。跨学科的正式和非正式教育活动将补充该研究，并将为经济弱势的布鲁克林社区的贫困学生提供机会。该研究项目旨在推进动物行为的计算模型，以改善临床前研究中的动物福利。具体来说，该奖项将通过基于实验的建模选择、通过严格的统计技术进行模型校准以及最终针对新实验的实验验证，建立斑马鱼行为的计算建模框架。该框架将基于随机微分方程，能够预测斑马鱼在二维和三维、幼虫和成虫、单个个体和群体中、在外部刺激存在下以及在精神活性化合物的作用下的运动。这种新颖的计算工具将用于评估以下可行性：根据模拟数据进行先验功效分析，选择解释变量，分析生物混杂情况下的再现性，以及无需实验即可推断实验结果。虽然该研究将主要依赖于现有的实验数据，但还将进行额外的实验来剖析显着的行为线索并证明计算机实验的潜力。

项目成果

An information-theoretic study of fish swimming in the wake of a pitching airfoil

鱼在俯仰翼型后游动的信息论研究

• DOI: 10.1016/j.physd.2019.02.014
• 发表时间: 2019-09
• 期刊: Physica D: Nonlinear Phenomena
• 作者: Zhang, Peng;Krasner, Elizabeth;Peterson, Sean D.;Porfiri, Maurizio
• 通讯作者: Porfiri, Maurizio

Modeling multi-sensory feedback control of zebrafish in a flow

模拟流动中斑马鱼的多感官反馈控制

• DOI: 10.1371/journal.pcbi.1008644
• 发表时间: 2021-01-01
• 期刊: PLoS Computational Biology
• 影响因子: 4.3
• 作者: D. A. Burbano;M. Porfiri
• 通讯作者: M. Porfiri

Application of symbolic recurrence to experimental data, from firearm prevalence to fish swimming

符号递归在实验数据中的应用，从枪支流行到鱼类游泳

• DOI: 10.1063/1.5119883
• 发表时间: 2019-11
• 期刊: Chaos: An Interdisciplinary Journal of Nonlinear Science
• 作者: Boldini, Alain;Karakaya, Mert;Ruiz Marín, Manuel;Porfiri, Maurizio
• 通讯作者: Porfiri, Maurizio

Can robotic fish help zebrafish learn to open doors?

机器鱼能帮助斑马鱼学会开门吗？

• DOI: 10.1117/12.2514289
• 发表时间: 2019-03
• 期刊: 2019
• 作者: Yang, Yanpeng;LeMay, Brandon;El Khoury, Rana;Clément, Romain J.;Ghirlanda, Stefano;Porfiri, Maurizio
• 通讯作者: Porfiri, Maurizio

Emergence of in-line swimming patterns in zebrafish pairs

斑马鱼对中直线游泳模式的出现

• DOI: 10.1017/flo.2021.5
• 发表时间: 2021-01
• 期刊: Flow
• 作者: Porfiri, Maurizio;Karakaya, Mert;Sattanapalle, Raghu Ram;Peterson, Sean D.
• 通讯作者: Peterson, Sean D.