Strategic Vision and Impact on Environmental HealthA. OverviewEnvironmental genomics focuses on the study of the gene-gene and gene-environment interactions thatmediate many of the complex diseases affecting human populations in today's world. This field combines theknowledge derived from modern human and molecular genetics with studies of mRNA, protein and metaboliteprofiling 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 ofbiological 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 beenfueled by the need to translate molecular knowledge into concepts that impact our day-to-day lives and thatimprove 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 molecularmedicine leading to the development of a strong infrastructure in DMA sequencing technologies, siRNArepositories, transcriptional profiling, mass-spectrometry (MS)-based protein analysis and proteomics, NMRandMS-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 emergingfrom 'omic technologies and facilitate translation of these findings to public health and clinical practice. Fullrealization of the benefits offered by molecular understanding of gene, protein and metabolite expressionprofiles, the molecular circuitry that integrates the biological response to environmental injury, and theidentification of novel biomarkers of disease, will require strong infrastructure support in the areas ofbioinformatics, 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 inenvironmental health. The UofL Center will promote scientific achievements that advance our molecularunderstanding of human diseases and the role of environmental factors in the pathogenesis of disorders ofcellular growth and differentiation. The thematic areas of scientific focus at UofL are environmentalcardiology, environmental carcinogenesis and developmental origins of health and disease. TheseNIEHS-funded areas of scientific activity are ripe for continued expansion and will be greatly facilitated by thecentralized infrastructure promoted by CEGIB. NIEHS investments at UofL will be leveraged by outstandinginstitutional commitments to continue support of core functions in transcriptional profiling, proteomics andmetabolomics and to establish clinical and epidemiological research centers. Concerted efforts over the nextfour years will be directed at the integration of disparate datasets to identify gene, protein and metabolitenetworks, the development of mathematical models to simulate and predict biological behavior, and theestablishment of productive partnerships between basic and clinical researchers that advance researchfindings in environmental genomics from the bench to the bedside. These efforts will help UofL environmentalhealth 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 naturalworld. If environmental health researchers are to sustain their impact in advancing the biomedical researchagenda in this country, an integrated way of thinking that 'marries' molecular biology to the higher levels ofbiological organization needs to be nurtured and cultivated among the environmental health researchcommunity. In this context, it is important to recognize that systems level thinking in environmental genomicsis not restricted to biomedical questions, but that it crosses over to the domains of clinical medicine and publichealth. Indeed, realization of the potential of 'omic technologies will require creation of structures that supportthe research enterprise and advance translation of molecular findings to practice. The team of UofLresearchers assembled in this application can contribute in meaningful ways to this goal.
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