Interdisciplinary partnerships in environmental health sciences.

The mission of the National Institute of Environmental Health Sciences (NIEHS) is to promote research that will ultimately reduce the burden of human illness and dysfunction from environmental causes. The research supported by the NIEHS addresses this mission through a diverse grants portfolio consisting of basic in vitro and animal research, population-based studies, and a limited number of patient-oriented studies that focus on the understanding, detection, prevention, and intervention of environmentally related disease and disease processes. Recent technological advances and a growing appreciation that environmental factors contribute to most complex diseases provide unprecedented opportunities for developing new research paradigms that bring together interdisciplinary teams of Scientists to move basic environmental health sciences research into clinical and public health practice.

The objective of this initiative is to foster scientific collaboration between clinical and basic investigators to accelerate the application of basic research results into the clinical setting to improve human health in those areas where environmental factors are known or expected to influence the development or progression of human disease. Scientific knowledge achieved through this research program is expected to move the field of environmental health sciences into new directions and approaches for the identification, treatment, and prevention of environmentally related diseases or disorders. Through this initiative, the NIEHS will support both the development of new collaborations between researchers with basic and clinical expertise and the continued efforts of existing collaborations. Both activities must directly support the integration of clinical and basic science research.

For the purpose of this solicitation, clinical research is defined as: 1) patient-oriented clinical research conducted with human subjects, or research on the causes and consequences of disease in human populations involving material of human origin (such as tissue or specimens) and for which an investigator or colleague directly interacts with human subjects in an outpatient or inpatient setting to clarify a problem in human physiology, pathophysiology, or disease; 2) development of new clinically based technologies, therapeutic interventions, or clinical trials; 3) epidemiologic and behavioral studies in humans; such studies are appropriate in cases where the primary focus of the study is on a specific disease or disorder and the clinical investigator is an essential part of the planning, conduct, and analysis of the study.

Basic science research is defined as mechanistic research using experimental approaches and may include use of cell lines, in vitro or in vivo models. Basic research may include the development of new tools to expand the capacity of clinically oriented research.

Applications to this solicitation may be either exploratory in nature, laying the foundation of long-term collaborations or attaining proof of principle for an innovative collaborative approach, or they may be continued development of established collaborations. In either instance, applications must focus on a specific human disease or disorder where there is evidence or a strong rationale for the involvement of environmental factors in its etiology or phenotypic expression and must involve research at both the basic and clinical levels. Suggested topics and example research projects include, but are not limited to, first, integration of basic mechanism-driven and clinical patient-oriented research to gain new insights into the role of environmental factors in complex human diseases: 1) integration of patient phenotype data with high data content techniques such as transcriptomics, proteomics, and metabolomics to investigate the mechanisms by which exposures lead to disease; 2) comparison of animal/model organism and human responses to toxicants to identify biological alterations contributing to the disease etiology; 3) examination of the impact of current and/or prior environmental exposures on the progression, treatment, and survival of patients with existing disease.

Second are collaborations between basic, patient-oriented, and epidemiologic researchers to identify and validate biomarkers and apply them to the development or progression of human diseases: 1) application of omics technologies and modeling to existing populations to identify predictive marker profiles for known exposures and the genesis of disease; 2) use of mechanistic response data obtained from the conduct of basic science experimentation to identify putative predictive markers of exposure and response and their validation in existing cohorts; 3) coordination of engineering and clinical expertise to develop systems that integrate exposure with individual biological response or phenotypic change; 4) innovative approaches to the identification of the determinants of individual susceptibility and the interaction between genes and environmental stressors in human disease.

Third is use of environmental stressors as a probe(s) to identify phenotypic variation in humans and animal models of disease to inform genetic analyses of disease susceptibility: 1) conduct of genome-wide association studies to study gene, gene-gene and gene-environment interactions in well characterized cases of environmentally induced disease; 2) identification and assessment of the functional relevance of SNPs and haplotypes associated with environmentally induced disease and the mechanistic consequences of those variations at the molecular and cellular levels.

Fourth are interdisciplinary approaches to the development of intervention and prevention strategies to alter the progression of environmentally induced human disease: 1) identification of novel compounds or engineering of biocompatible materials that protect against, inhibit, or reverse toxicant actions and their validation in disease relevant settings; 2) development of mechanistically derived prevention strategies and application of them in populations with known genetic susceptibility to environmental stressors.

Fifth is collaborative development or refinement and application of model systems that faithfully replicate human disease condition or species comparisons that can be used to understand environmentally induced human disease processes. NIEHS encourages applicants to utilize existing biological and or other resources to address the topics described above where applicable, such as: 1) new analyses of data from completed studies; 2) assay of archived biological samples from completed and ongoing studies; 3) collection of new data and samples from ongoing or completed studies; 4) analysis of public and other accessible databases.

Proposals addressing perturbation of biological processes in the absence of extension to human disease will be considered nonresponsive in the context of this solicitation.

This funding opportunity will use the NIH Exploratory/Developmental Grant (R21) and Research Project Grant (R01) award mechanisms. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/ grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for nonmodular research grant applications.

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/ phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo at 301-435-0714 (telecommunications for the hearing impaired: TTY 301-451-0088) or by e-mail: [e-mail]

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling 866-705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The letters of intent receipt dates for this PAR are December 11, 2005, 2006, 2007, with the application receipt dates January 11, 2006, 2007, 2008. The complete version of this PA is available at http://grants/guide/pa-files/PAR-05-168

Contact: Cindy Lawler, Cellular, Organs and Systems Pathobiology Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-23, Research Triangle Park, NC 27709 USA, 919-316-4671, fax: [phone], e-mail: [e-mail]; Kimberly Gray, Susceptibility and Public Health Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-21, Research Triangle Park, NC 27709 USA, 919-541-0293, fax: [phone], e-mail: [e-mail]. Reference PAR-05-168