Strategic Vision & Impact on Environmental Health

战略远景和对环境健康的影响 A.概述 环境基因组学的重点是研究基因-基因和基因-环境的相互作用， 在当今世界上，许多影响人类的复杂疾病都是由它介导的。该字段结合了 从现代人类和分子遗传学中获得的知识，包括mRNA，蛋白质和代谢物的研究 分析，以了解基因和遗传变异如何与环境因素相互作用，导致疾病。 整合生物学是一个密切相关的领域，专注于应用系统理论来研究 生物学行为和途径对保持健康或疾病的发作和进展至关重要。 环境基因组学和综合生物学领域的进展，在过去的五年中， 由于需要将分子知识转化为影响我们日常生活的概念，并且 改善环境医学和公共卫生实践。为此，路易斯维尔大学（UofL） 研究人员在遗传学和分子生物学领域实施了学术和研究计划， 医药导致了DMA测序技术，siRNA的强大基础设施的发展 存储库、转录谱分析、基于质谱（MS）的蛋白质分析和蛋白质组学、NMR和 基于MS的代谢组学，以及最近的生物信息学。 联邦政府资助的环境基因组学和综合生物学中心（CEGIB） 将帮助环境健康研究人员管理和解释出现的数据 并促进将这些发现转化为公共卫生和临床实践。充分 实现对基因、蛋白质和代谢物表达的分子理解所带来的益处 概况，分子电路，整合生物反应，环境伤害，和 确定新的疾病生物标志物，将需要在以下领域提供强有力的基础设施支持： 生物信息学、生物统计学、计算生物学和实验室到临床或实验室到社区整合。 在本申请中，我们寻求资金创建国家环境健康科学研究所（NIEHS） UofL的核心中心，专注于基因组学和整合生物学应用于 环境卫生。UofL中心将促进科学成就，推动我们的分子 了解人类疾病和环境因素在疾病发病机制中的作用， 细胞生长和分化。在UofL科学重点的主题领域是环境 心脏病学、环境致癌作用以及健康和疾病的发育起源。这些 NIEHS资助的科学活动领域已经成熟，可以继续扩大，并将得到 CEGIB推动的集中式基础设施。NIEHS在UofL的投资将被优秀的 机构承诺继续支持转录谱分析、蛋白质组学和 代谢组学和建立临床和流行病学研究中心。下一个共同努力 四年的时间将致力于整合不同的数据集，以确定基因、蛋白质和代谢物 网络，数学模型的发展，以模拟和预测生物行为，以及 在基础研究人员和临床研究人员之间建立富有成效的伙伴关系， 环境基因组学的发现从实验室到临床。这些努力将有助于UofL环境 健康科学研究人员仍然具有竞争力，并处于生物医学研究的前沿。 生物的复杂性也许只不过是自然界固有的复杂性的反映。 世界如果环境健康研究人员要保持他们在推进生物医学研究方面的影响， 在这个国家的议程，一个综合的思维方式，“婚姻”分子生物学的更高水平， 在环境健康研究中需要培育和培育生物组织 社区在这种情况下，重要的是要认识到，环境基因组学中的系统级思维 它不仅限于生物医学问题，而且跨越了临床医学和公共卫生领域。 健康事实上，要实现“组学技术”的潜力，就需要建立支持 研究企业和先进的分子发现转化为实践。UofL团队 参加这一申请的研究人员可以以有意义的方式为这一目标作出贡献。

Strategic Vision and Impact on Environmental Health A. Overview Environmental genomics focuses on the study of the gene-gene and gene-environment interactions that mediate many of the complex diseases affecting human populations in today's world. This field combines the knowledge derived from modern human and molecular genetics with studies of mRNA, protein and metabolite profiling to understand how genes and genetic variations interact with environmental factors to cause disease. Integrative biology is a closely related field focused on the application of systems theory to the study of biological behavior and pathways critical to the preservation of health or the onset and progression of disease. Advances in the fields of environmental genomics and integrative biology during the past five years have been fueled by the need to translate molecular knowledge into concepts that impact our day-to-day lives and that improve the practice of environmental medicine and public health. To this end, University of Louisville (UofL) researchers have implemented academic and research programs in the areas of genetics and molecular medicine leading to the development of a strong infrastructure in DMA sequencing technologies, siRNA repositories, transcriptional profiling, mass-spectrometry (MS)-based protein analysis and proteomics, NMRand MS-based metabolomics, and more recently, bioinformatics. The establishment of a federally-funded Center for Environmental Genomics and Integrative Biology (CEGIB) at UofL will help environmental health researchers with the management and interpretation of data emerging from 'omic technologies and facilitate translation of these findings to public health and clinical practice. Full realization of the benefits offered by molecular understanding of gene, protein and metabolite expression profiles, the molecular circuitry that integrates the biological response to environmental injury, and the identification of novel biomarkers of disease, will require strong infrastructure support in the areas of bioinformatics, biostatistics, computational biology and bench-to-bedside or bench-to-community integration. In this application, we seek funding to create a National Institute of Environmental Health Sciences (NIEHS) Core Center at UofL that focuses on the application of genomics and integrative biology to problems in environmental health. The UofL Center will promote scientific achievements that advance our molecular understanding of human diseases and the role of environmental factors in the pathogenesis of disorders of cellular growth and differentiation. The thematic areas of scientific focus at UofL are environmental cardiology, environmental carcinogenesis and developmental origins of health and disease. These NIEHS-funded areas of scientific activity are ripe for continued expansion and will be greatly facilitated by the centralized infrastructure promoted by CEGIB. NIEHS investments at UofL will be leveraged by outstanding institutional commitments to continue support of core functions in transcriptional profiling, proteomics and metabolomics and to establish clinical and epidemiological research centers. Concerted efforts over the next four years will be directed at the integration of disparate datasets to identify gene, protein and metabolite networks, the development of mathematical models to simulate and predict biological behavior, and the establishment of productive partnerships between basic and clinical researchers that advance research findings in environmental genomics from the bench to the bedside. These efforts will help UofL environmental health science investigators remain competitive and at the cutting edge of biomedical research. Biological complexity is perhaps nothing more than a reflection of the complexities inherent to the natural world. If environmental health researchers are to sustain their impact in advancing the biomedical research agenda in this country, an integrated way of thinking that "marries" molecular biology to the higher levels of biological organization needs to be nurtured and cultivated among the environmental health research community. In this context, it is important to recognize that systems level thinking in environmental genomics is not restricted to biomedical questions, but that it crosses over to the domains of clinical medicine and public health. Indeed, realization of the potential of 'omic technologies will require creation of structures that support the research enterprise and advance translation of molecular findings to practice. The team of UofL researchers assembled in this application can contribute in meaningful ways to this goal.