Microarrays in Fathead Minnows and Bass

描述(申请人提供)：微阵列是测量环境中污染物的生物影响的一种强有力的方法。因为它们被用来同时测试许多基因表达的变化，它们提供了关于化合物比目前使用的方法更快地影响健康的机制的数据，这使得它们比目前的测试成本低得多。今天，基因芯片(微阵列)是人类疾病研究中的一项成熟技术。我们刚刚完成的第一阶段资助的目的是将它们的力量和精确度带到环境毒理学领域。通过了解污染物如何影响鱼类和其他野生动物的基因表达，我们可以开始将环境暴露与这些动物的不利健康影响联系起来，并通过外推将其与人类联系起来。在这个第二阶段的提案中，EcoArray打算开发、验证和开始销售基于寡核苷酸的大型玻璃微阵列，用于愚头鱼和大口黑鱼，并开发一个强大的数据库的主干。在第三阶段，我们将利用从这笔赠款中获得的知识，最终确定我们提供的一套通用和特殊用途的微阵列，用于学术界、政府和工业界的研究和环境监测。我们成功的第一阶段赠款验证了针对一小部分环境污染物的阵列的使用，并产生了两个物种的原型阵列，如我们的出版物、演示文稿和海报中所述。我们这项第二阶段工作的目标是将目前的阵列扩展到更大、更健壮的格式，从而产生10,000+基因的肥头小鱼微阵列和2,000+基因的大嘴巴鱼微阵列。我们聘请了五名合作者，他们都是鱼类生物学方面的专家，对愚头鱼或大口黑鱼进行暴露和野外分析。对于肥头小鱼的研究，我们将使用我们将开发的微阵列来识别和表征在超级基金网站上常见的14种不同化合物的遗传特征，这些化合物已知具有不同的作用模式。其中许多化合物被列入2003年综合环境反应、补偿和责任法案(CERCLA)的优先名单。我们目前正在与美国环保局合作(CRADA)，挑选最佳的微阵列平台并验证其使用，这个商业平台将成为我们增强型微阵列的基础。我们将把基因表达数据合并到一个关系数据库中，该数据库还将包括其他参数，如水化学数据和处理物种中的生物和生理终点。我们将进行类似的实验室和实地研究，但规模较小，在大口黑鱼，并识别和表征5种不同化合物的遗传特征。我们已经开始了我们的营销计划，并在销售与基因发现相关的实验室服务方面取得了初步成功。我们预计将在2005年底提供与美国环保局共同开发的基于寡核苷酸的芯片，然后在2006年底开始我们在这笔赠款中开发的芯片以及其他几种补充产品的营销推出。

DESCRIPTION (provided by applicant): Microarrays are a powerful way to measure the biological impact of contaminants in the environment. Because they are used to test changes in expression of many genes in parallel, they provide data on the mechanisms by which compounds affect health more quickly than methods now in use, which makes them much less expensive than current tests. Today, gene chips (microarrays) are an established technology in human disease research. The purpose of the Phase I grant we just completed and this proposed continuation is to bring their power and precision to environmental toxicology. By understanding how contaminants affect gene expression in fish and other wildlife, we can begin to link environmental exposures to adverse health effects in these animals and by extrapolation, to humans. In this Phase II proposal, EcoArray intends to develop, validate and begin to market large oligonucleotide-based glass microarrays for fathead minnows and largemouth bass and develop the backbone of a powerful database. In Phase III, we will use knowledge obtained in this grant to finalize our product offering of a suite of general- and special-purpose microarrays for research and environmental monitoring by Academia, Government and Industry. Our successful Phase I grant validated the use of arrays for a small set of environmental contaminants and resulted in prototype arrays for the two species, as described in our publications, presentations and posters. Our goal for this Phase II work is to expand the current arrays to a larger, more robust format, resulting in a 10,000+-gene fathead minnow microarray and 2,000+ gene largemouth bass microarray. We have engaged five collaborators, all of whom are experts in fish biology, to carry out exposures and field analysis in fathead minnows or largemouth bass. For the fathead minnow studies, we will use the microarrays that we will develop to identify and characterize the genetic signatures for 14 different compounds commonly found at superfund sites, and that are known to have distinct modes of action. Many of these compounds are on the 2003 Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Priority list. We are currently involved in a collaboration (CRADA) with the EPA to pick the best microarray platform and validate its use, and this commercial platform will be the basis for our enhanced microarrays. We will incorporate the gene expression data into a relational database that will also include other parameters such as water chemistry data and biological and physiological endpoints in the treatment species. We will conduct similar laboratory and field studies, but on a smaller scale, in largemouth bass and identify and characterize the genetic signatures for 5 different compounds. We have begun our marketing plan, and have had early success in selling laboratory services associated with gene discovery. We expect to offer an oligonucleotide-based chip developed with the EPA in late 2005 and then begin our marketing launch of the chips developed in this grant, as well as several other complementary products, in late 2006.