CONSORTIUM OF LUNG REPAIR AND REGENERATION: BUILDING THE FOUNDATION (U01): RFA-HL-12-006
Also note: Lung Repair and Regeneration Consortium Administrative Coordinating Center (U01): RFA-HL-12-010
Details at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-010.html
Components of Participating Organizations
National Heart, Lung, and Blood Institute
Application Receipt Date(s): February 10, 2011
The National Heart, Lung, and Blood Institute (NHLBI) invites applicants to participate in the Lung Repair and Regeneration Consortium (LRRC). The goal of the Consortium is to bring together multidisciplinary teams of investigators, cutting edge technologies, innovative strategies, and new ideas to catalyze research on the mechanisms of lung regeneration and repair, and to develop new tools, reagents, and models to elucidate the lung's capacity for regeneration. The Consortium will also contain collaborative research support and skills development components to be administered after the Consortium is assembled through the companion FOA, RFA HL-12-010 "Lung Repair and Regeneration Consortium (U01) Administrative Coordinating Center" in years 27-5. The purpose of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data, and resources to move the field of lung regeneration forward toward development of new therapies for human diseases. This FOA solicits Research Project Cooperative Agreement (U01) applications from institutions/organizations that propose 1) to test innovative hypotheses of mechanisms that control adaptive and maladaptive lung repair/regeneration after injury and include studies to validate these mechanisms are relevant in humans and 2) to develop two or more novel tools (e.g. reagents, models, imaging, and/or data analysis tools) that would accelerate research progress in lung regeneration. LRRC Research Centers will be comprised of multidisciplinary teams that will work collaboratively with other Research Centers in the LRRC to accelerate science in lung repair and regeneration.
Collaboration and interaction between LRRC investigators will be a requirement of the program. The LRRC will be responsible for collaboratively generating, validating, and sharing necessary reagents, models, antibodies, assays, protocols, and technologies that are beyond the scope of any single research effort with the goal of accelerating lung repair/regeneration research specifically, but also the potential to advance basic research in general. These tools and reagents will be rapidly shared with members of the Consortium, and eventually advertised and made available on a public website developed by the Administrative Coordinating Center.
The goal of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data, and resources to move the field of lung regeneration forward. The Consortium will consist of up to six Research Center projects funded through this FOA, and an Administrative Coordinating Center (ACC) supporting the Consortium funded through a separate FOA, RFA-HL-12-010 http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-010.html. The ACC will also administer funds available in years 2-5 to support collaborative studies and resource validation studies across participating sites in the Consortium and a Skills Development Core in tissue regeneration. Collaboration and interaction among LRRC investigators will be a requirement of the program and will be facilitated with a website, teleconferences, and biannual meetings of the investigators organized by an Administrative Coordinating Core (ACC).
A major goal of the Lung Repair and Regeneration Consortium is to foster highly innovative, high-risk approaches that are not easily funded by traditional mechanisms and that have the potential for unusually high impact that could significantly advance the field. Solicitations for collaborative studies across two or more Consortium Research Centers will be initiated beginning in Year 1 by the ACC with project support for 1-3 years with approximately $100,000-$150,000 direct costs per year starting in year 2. The studies are also expected to be helpful in developing young investigators and may bring in outside experts. The External Advisory Committee will be responsible for peer review of these new collaborative studies. Progress on these studies will be monitored by NHLBI program staff.
As new resources such as reagents, models, and tools are developed by individual Research Centers, confirmation of the application of these will be fostered through solicitations for resource validation by other Research Centers in the Consortium. Beginning in Year 2, solicitations for resource validation studies will be issued by the ACC at direct costs of approximately $50,000-$150,000 for one year. The External Advisory Committee will be responsible for peer review of these new validation studies. Progress on these studies will be monitored by NHLBI program staff.
Each Research Center will be responsible for participation in a Skills Development Core, coordinated by the ACC, that helps young investigators develop skills and experience to progress to more senior status in the field of lung regenerative medicine. The Skills Development Core will support travel and costs for supplies and equipment to support developmental activities, courses, seminars, workshops, and other activities directly related to the development plan for junior investigators across the Consortium. A Skills Development Committee, composed of an investigator from each Research Center and from the ACC, will develop and coordinate activities among the Research Centers to enhance skills development for graduate students, postdoctoral fellows, and young faculty. Each application should identify a Skills Development Coordinator, whose relevant experience is well documented in the Research Plan. The budget must include support for a minimum of 2.4 calendar months effort for the applicant PI or a minimum of 2.4 calendar months combined effort for all PIs if the multiple PI strategy is used. The budget should identify an individual with experience in skills development who will serve as representative on the Skills Development Committee. This individual should declare a minimum effort of 0.6 calendar months specifically for skills development activities, in addition to any research activities undertaken by the individual.
The LRRC will have a Steering Committee that will be responsible for overall scientific direction, coordination, and oversight. The Steering Committee will be composed of the Lead PI/PDs for each Research Center, the ACC PI/PD, and the NHLBI Project Scientist. The Steering Committee will be chaired by an investigator selected by the NHLBI. The Steering Committee will meet in person for an implementation meeting at the start of the project period, by conference call at least quarterly, and in person at least twice a year throughout the project period (one of these meetings at the Annual Grantee Meeting-see below). Participation in Steering Committee activities is a requirement of at least one PI/PD from each Research Center. Funds should be requested to attend Steering Committee meetings as well as other collaborative meetings of the LRRC.
An External Advisory Committee (EAC) will oversee the Consortium. The Committee will consist of non-Consortium affiliated scientists and other experts appointed by the NHLBI to provide annual reviews of progress, and serve as the peer review panel for collaborative studies.
The ACC will arrange annual meetings to encourage the exchange of information for the LRRC. In the preparation of the budget for the grant application, applicants should include travel funds for one meeting each year to be held in or near Bethesda, MD, for the Principal Investigators, key collaborators, and trainees. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents. At the meetings, participants will discuss quality assurance, bioinformatics, coordination, sharing, and a means of informing the community about progress made by the Consortium.
The ACC will serve a range of functions such as organizing meetings; arranging teleconference calls of the Steering Committee, External Advisory Committee, and Consortium annual meeting; and designing and maintaining written materials and websites to support the Consortium. The ACC will be responsible for solicitation of applications for collaborative pilot studies and tool validation studies. The ACC will oversee the review and award of collaborative funds for the Consortium, award subcontracts for these funds, assist in the Skills Development Core, and coordinate the submission of progress reports by the awardees for review by the External Advisory Committee and NHLBI staff.
During the course of the funding period, technologies will improve and the rate of progress and scope of the research may change. It is expected that the Principal Investigators, in consultation with NHLBI program staff, will make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, and to maintain excellent coordination with the other projects funded under this RFA.
All applications submitted through this announcement and the companion FOA (RFA-HL-12-010) must include technology transfer and sharing plans for both data and unique research resources that are generated by the projects in concordance with NHLBI/LRRC policies. It is expected that resources developed by the LRRC will be made available to the broader scientific community, after a propriety period, at no charge other than the cost of reproduction and distribution. Applicants must indicate their willingness to distribute research tools to the wider community including antibodies, transgenic mouse strains, microarray data, and other reagents. A distribution plan should be included in the application. Likewise, applicants must describe their willingness to submit microarray data generated through this project and other pertinent information about research resources generated through this U01 to the LRRC Coordinating Center as the resources are developed.
Selected Research Examples include but are not limited to:
Use novel lung repopulation models and humanized animal models that allow functional assessment of how putative progenitor or other cells respond to promote repair and regeneration. Studies based solely on immunostaining of banked tissue sections for human studies would not be acceptable under this FOA.
Initiate new collaborations with tissue and bio-engineers to investigate use of novel scaffolds and biomaterials to study mechanisms of lung repair and regeneration. Utilize tissue engineering strategies to modify the endogenous lung microenvironment to identify local determinants and regulators of lung regeneration.
Apply induced pluripotent stem cell research or cell directed therapies using putative progenitor cell populations to deliver transcription factors or other molecules of interest in order to elucidate mechanisms of lung repair/regeneration.
Elucidate the influence of the microenvironment on progenitor cell self-renewal and differentiation.
Investigate the use of novel transcription factors for cell expansion and differentiation. Investigate mechanisms controlling cell fate decisions and self-renewal after injury and the potential for cell plasticity of resident lung cells.
Identify molecules and pathways signaling adaptive and maladaptive responses after injury in animal models and validate findings of key signaling pathways involved in human lung regeneration.
Determine developmentally dependent changes in histone methylation, histone acetylation and DNA methylation, during reparative responses to injury.
Selected Tool Development examples include but are not limited to:
Develop models to lineage trace individual cell types in the epithelium, endothelium, and/or mesenchyme that contribute to lung repair/regeneration.
Develop nanoscale and microscopy methods to study progenitor cell markers on lung epithelial, endothelial, mesenchymal compartments.
Develop genetic cell marking technology for lung epithelial cell lineages over the course of development, structural growth, repair and regeneration.
Develop tools to identify subphenotypes of lung cells based on molecular signatures during maintenance and repair after injury.
Develop novel functional assays of "stemness" for lung.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-006.html.
GETTING FROM GENES TO FUNCTION IN LUNG DISEASE, NHLBI (R01): PA-11-011
Components of Participating Organizations
National Heart, Lung, and Blood Institute
Application Receipt/Submission Date(s): February 5, 2011, by 5:00 PM local time of applicant organization
AIDS Application Due Date: May 7, 2011
This FOA issued by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, encourages Research Project Grant (R01) applications from institutions/organizations that propose to characterize the function of genes(s) and their associated variants identified by genome-wide association studies (GWAS) or other genetic approaches to be involved in lung diseases. Studies should use integrated approaches across scientific disciplines to determine the pathobiological function of these genes.
Recent genetics studies of asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, idiopathic pulmonary fibrosis (IPF), and other lung-relevant phenotypes have clearly shown the usefulness of genome-wide association studies (GWAS) for gene discovery. Many genes or chromosomal regions have already been associated with lung dysfunction, and the number of related genes is expected to increase markedly over the next year as the results of ongoing meta-analyses and resequencing studies are published. In addition to genes already considered as candidates (e.g., RAD50, which is in the same linkage block as IL13, FcERA, TSLP), GWAS results have suggested involvement of many novel genes about which little is known. The identification of novel genes is especially significant because these may point to pathways and mechanisms not previously recognized in lung diseases. There now exists an exciting possibility that follow-up studies of pathways and mechanisms related to these genetic variants may quickly generate knowledge that leads to novel and more effective ways to prevent and treat a variety of pulmonary conditions. However, in many cases, the functions of the identified genes and their variants, and the mechanisms by which they may contribute to lung diseases are completely unknown.
A critical next step is to elucidate the biological functions of these genes and their variants in the lung. Fortunately, the experimental approaches and tools required for this are readily available, including genetic manipulations of in vitro and animal models; -omics measures; systems biological analyses; eQTL analyses; and human studies of gene-gene interactions, epigenetic variations, and evoked biomarker phenotypes. Nevertheless, progress in getting from genes to function in pulmonary diseases has been remarkably slow. A major impediment to progress appears to be the requirement for diverse, multidisciplinary investigative teams. Very few existing groups can bridge from genetics to molecular biology to cell physiology to disease as is required to learn how a particular genetic variant affects molecular and cellular function in a way that promotes disease. Furthermore, studies of different genetic variants often require very different experimental approaches, model systems, and investigative teams, based on what is already known about the genetic region and the pulmonary condition. Each genetic variant may require a unique team and research plan for follow-up, and this is properly considered high-risk research by grant reviewers. A FOA is needed to bring this pivotal research effort to the forefront, to bring biology into what has to date been a purely genetic exercise, and to build the necessary research teams critical to ensuring successful attainment of the research goals.
The purpose of this initiative is to accelerate research in functional genetics of lung diseases by supporting follow-up functional studies of particular genetic variants that have been linked to pulmonary conditions. Each study will use a multidisciplinary team to investigate the function of a single genetic variant or a small number of related genes. Applicants will be encouraged to employ genomic and system genetic approaches and integrate studies of individual genes with pathways and regulatory networks, using a variety of model systems. However, the initiative will not be limited to particular experimental methods but will allow investigators to employ a wide variety of investigative approaches, ranging from exploration in model systems to proof of concept studies with human biospecimens. Investigators may focus on one lung disease or may investigate a single genetic variant across lung diseases. Because a major bottleneck to this research has been the need to build diverse, multidisciplinary investigative teams that cross scientific disciplines, this program strongly encourages the forging of new collaborations among top-tier pulmonary and non-pulmonary investigators in different scientific disciplines (system genetics, informatics, various model systems) and building diverse, multidisciplinary teams that integrate genetics, molecular biology, cell physiology, and bioinformatics to bear on this problem. Investigator meetings will be held yearly to enable investigators to share their successes and challenges with the varied approaches being used to explore how the genetic variation results in functional changes and how the genes are involved in lung disease pathogenesis.
Through this program, we expect to gain mechanistic understanding of: (1) what these genes do, (2) how the genetic variation influences gene expression or function, and (3) how particular genes and specific variants are involved in lung disease pathogenesis. Development of new technologies, tools, and model systems will be allowed if required to address the specific questions being asked in the research proposal.
Research related to each of these categories should be addressed using integrated approaches across disciplines (genetics, bioinformatics, systems biology, and phenotype/clinical) and should utilize appropriate technologies such as "-omics," systems genetics/biology and pathway/network analysis, animal models of lung disease, human studies in ethnically/racially diverse populations, and mining of data from existing resources. The latter could include, but is not limited to, data from clinical trial cohorts and population-based cohorts, studies of transcriptional and proteomic profiling in relevant tissues, animal models of lung disease, and repositories of banked tissues.
Research topics to be addressed as part of this initiative include, but are not limited to:
Functional characterization of genes (and variation) identified by GWAS to be involved in the pathogenesis of lung disease using integrated -omic (genetics, genomics, transcriptomics, proteomics, metabolomics, phenomics, etc) approaches across scientific disciplines (genetics, bioinformatics, systems biology, and phenotype/clinical) aimed at determining the mechanism by which genetic variation affects lung disease (potentially through gene x gene, gene x environment, epigenetics, integrated/comparative approaches).
Exploration of the role of the environment and mechanisms of transcriptional regulation (eQTLs and epigenetic modifications) of identified genes including examining changes over time/development in different cell types and in response to environmental stimuli in humans and mice and other appropriate model systems, and by incorporating systems genetics and network building.
Development of model systems (including mice, flies, zebrafish, worms, and yeast) and high throughput functional screening methods to assess how lung disease-related genes function in complex biological systems. This can include com parative genomics and phenomics to understand gene function in other targets.
Exploration of the contribution of the lung disease-related variants to abnormalities in gene expression or function in biospecimens from human or animal disease models as proof of concept.
Application of integrative systems biology, genomic, and bioinformatic approaches for comprehensive mining of existing data sets to identify novel genes (and associated variants) and pathways involved in lung disease including in silico studies of function or putative function for prioritizing variants or genes after GWAS to inform the types of functional studies to pursue.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-011.html.
TOWARD AN IMPROVED UNDERSTANDING OF HDL FUNCTION, NHLBI (R01): PA-11-012
Components of Participating Organizations
National Heart, Lung, and Blood Institute
Application Receipt/Submission Date(s): February 5, 2011, by 5:00 PM local time of applicant organization
AIDS Application Due Date: May 7, 2011
The purpose of this Funding Opportunity Announcement (FOA) is to develop, validate, and standardize assays to measure HDL function and biomarkers for HDL function and to identify novel genes, pathways, and potential therapeutic targets in relation to HDL function.
Epidemiological studies demonstrating a strong association of lipid levels with atherothrombotic events suggest the therapeutic potential of lipid-targeted therapy. The benefit of lowering LDL is well demonstrated in many randomized trials. Current understanding suggests that therapeutic manipulation of HDL should also be useful in reducing cardiovascular risk. For instance, animals infused with HDL particles and transgenic mice overexpressing the major HDL apolipoprotein, apoA-I, have shown a marked reduction in atherosclerosis. In addition, small studies in humans using coronary intravascular ultrasound (IVUS) suggest that infusion of reconstituted HDL particles is associated with regression of atherosclerosis. However, despite substantial experimental support, there are as yet no randomized trials demonstrating a benefit of HDL-targeted therapy. In fact, the failure of torcetrapib (an inhibitor of cholesterol ester transfer protein (CETP)) to be beneficial, despite raising HDL levels, has generated concern about HDL therapy more generally. This failure underscores the incompleteness of our fundamental understanding of HDL function rather than a lack of therapeutic potential of HDL manipulation.
In addition, genetic and other studies in humans indicate the complexity in the relationship of HDL to atherosclerosis. Naturally occurring genetic conditions in humans indicate that lower HDL-C values are not uniformly associated with excess cardiovascular risk. Also, higher HDL-C levels may not always confer a protective benefit. These data emphasize the importance of HDL function.
HDL particles are heterogeneous in shape, density, size, composition and have multiple functional properties such as reverse cholesterol transport (RCT), as well as anti-oxidant, anti-inflammatory, and antithrombotic activities. Promotion of cholesterol efflux from macrophages, its return to the liver and ultimately biliary excretion, completing the pathway of RCT, is thought to be one of the most important mechanisms by which HDL protects against atherosclerosis. Recent research highlights other functional properties of HDL as mentioned above as well.
Currently, there are no standard methods to assess HDL function in humans. Macrophage-specific assays have been useful in mice; however, their applicability to humans remains uncertain. Developing robust, reliable, and reproducible assays to assess HDL function in humans will allow early assessment of changes in HDL functionality in response to new HDL-targeted therapies. Assays for other HDL functional properties such as anti-oxidant and anti-inflammatory effects are needed as well. There is a major need to study HDL and its role in atherogenesis, especially in developing and validating HDL functional assays and elucidating mechanisms of HDL function from recent studies such as information from genome-wide association studies (GWAS) by multidisciplinary and collaborative research.
The ultimate goal of this FOA is to develop reproducible and robust assays to measure HDL function and to identify novel genes and pathways related to HDL function.
To address this goal, research projects prompted by this FOA are expected to advance such areas as:
Development of methods to measure in vivo RCT, particularly in humans and other properties of HDL function such as anti-Inflammatory and antioxidant activity, and modulation of endothelial function.
Validation of new biomarkers for HDL function. For instance, correlation of assays such as cholesterol efflux capacity of serum with carotid IMT or other measures of subclinical and clinical atherosclerosis.
Identification of proteins (beyond apolipoproteins) in HDL that could serve as biomarkers for HDL function and cardiovascular disease using proteomics strategy such as mass spectrometry, protein arrays, and other quantitative techniques. This will link the HDL proteome to HDL function.
Elucidation of metabolic pathways and mechanisms of novel genes related to HDL function.
Delineation of HDL action on monocyte-macrophages at different stages of atherogenesis.
Understanding the mechanisms linking HDL to preservation of endothelial function.
To maximize the likelihood of success, projects that bring together experts in multidisciplinary fields such as clinical chemists, biochemists, cell and molecular biologists, geneticists, physiologists, and clinicians are encouraged. Projects leveraging NHLBI and industry randomized trials, with their large, well-characterized patient populations, are encouraged as well.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American Tribal Governments (other than federally recognized); U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-012.html.
SICKLE CELL DISEASE: INFLAMMATION, THROMBOSIS AND VASCULAR DYSFUNCTION, NHLBI (R01): PA-11-013
Components of Participating Organizations
National Heart, Lung, and Blood Institute
Application Receipt/Submission Date(s): February 5, 2011, by 5:00 PM local time of applicant organization
AIDS Application Due Date: May 7, 2011
This Funding Opportunity Announcement (FOA) encourages grant applications for research that will lead to a better understanding of the role of the immune and coagulation systems in the vaso-occlusive pathologies associated with Sickle Cell Disease (SCD). Seeing SCD as a purely red cell disorder does not explain all the pathophysiological processes that contribute to clinical representation of this disease. For example, circulating sickle cells may initiate vaso-occlusion by their interactions with endothelium, granulocytes, platelets and each other. Current achievements in both leukocyte and platelet biology offer the potential for dramatic progress in the understanding of their interface with SCD. Collaborative studies that involve a team effort of SCD investigators and researchers from biochemical, biophysical, and immunological fields are needed to identify new pathways and regulatory mechanisms that may be as important in the pathophysiology of SCD as red blood cell sickling itself.
This FOA is designed to stimulate multidisciplinary and new collaborations in SCD, thus collaboration of SCD researchers or clinicians with investigators in platelet, leukocyte, vascular biology, or immunology is required (as a part of a multi-PI application) to meet the objectives of this PA. A further objective is to encourage additional investigators outside the traditional SCD field to begin work on SCD.
Applications are sought from cell and vascular biologists to identify new targets that would improve the therapeutic options for SCD patients. Areas of interest and appropriate topics include but are not limited to those listed below:
Investigate the mechanism(s) of the SCD phenotype(s).
Determine how cell-cell interactions regulate hemolysis in SCD. Cell-cell interactions include: Reticulocytes-Leukocytes; Reticulocytes-Platelets; Platelets-Leukocytes; Microparticles-Target Cells (Reticulocytes, Leukocytes, and Platelets); and Interactions with Endothelial Cells
Examine how cell-cell interactions alter gene expression patterns in SCD.
Understand SCD human physiology and measure physiological responses noninvasively in patients and SCD animal models.
Identify and validate surrogate endpoints.
Image what is going on during pain crises in SCD patients-i.e. RBC aggregation, blood flow regulation.
Investigate coagulation activation in acute vaso-occlusive SCD events.
Investigate coagulation signaling mechanisms that promote lung injury, inflammation and vascular repair in SCD.
Use systems biology approaches to study SCD.
A community of investigators who are in touch with each other should partner with experts in other fields such as engineering.
Understand the role of the autonomic nervous system in SCD patients.
Ensure that pilot studies can be launched and completed.
Identify and test novel therapeutic ideas.
For all SCD clinical trials, identify what worked correctly and what went wrong.
Use multi-modality therapy to treat SCD.
If single-modality therapy is studied, an endpoint must include vascular efficacy.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-013.html.
HIV INFECTION OF THE CENTRAL NERVOUS SYSTEM (R01): PA-11-014
Components of Participating Organizations
National Institute of Mental Health
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse
National Institute of Neurological Disorders and Stroke
Application Receipt/Submission Date(s): Multiple receipt dates, see announcement
The National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA), and the National Institute of Neurological Disorders and Stroke (NINDS) invite research grant applications focused on defining the pathogenic mechanisms involved in Human Immunodeficiency Virus (HIV)-1 Associated Neurocognitive Disorders (HAND) and, identifying therapeutic strategies to treat and prevent the neurobehavioral and neurological effects of HIV-1 on the central nervous system (CNS). Applications ranging from basic research to clinical diagnosis and treatment in domestic and international settings are of interest. Multidisciplinary research teams and collaborative alliances are encouraged but not required.
The research areas that are pertinent to this FOA include, but are not limited to:
Evolving Mechanisms of HIV Neuropathogenesis in the HAART era
Study the impact of low level viral replication and immune activation (in CNS compartment) on HIV neuropathogenesis in the setting of high CD4 counts in the periphery;
Study the role of adaptive and innate immunity in regulating anti-viral responses in the CNS compartment, and the effects of substance abuse on this regulation;
Define the mechanisms regulating fluctuating patterns of CNS symptomatology in the HAART era;
Identify novel molecular markers linked with milder and chronic forms of HIV-associated CNS disease using state-of-the art techniques including genomics, proteomics, metabolomics, systems biology and neuroimaging;
Define novel pathways leading to neuronal toxicity in the HAART era. These could include autophagy, novel inflammatory mediators, viral factors, excitotoxicity and signaling pathways;
Define the pathways and mechanisms leading to synaptodendritic degenerative changes in the setting of chronic HIV infection, and the protective vs. pathogenic effects of those changes;
Assess the impact of metabolic changes relating to HAART on neurocognitive outcomes among HIV-1 infected patients. These include studies on the effect of insulin resistance, lipid abnormalities and mitochondrial dysfunction on HIV-associated CNS disease;
Study mechanisms involved in CNS manifestations of HIV-associated immune reconstitution inflammatory syndromes;
Study changes in neuronal excitability, synaptic plasticity, and neural circuit activity that contribute to the development of HAND; and
Determine the impact of drugs of abuse, or related receptor signaling pathways or circuits, on the cellular and molecular mechanisms underlying HAND, including HIV trafficking to the CNS, neuron-glial communication, neurophysiologic changes and excitability, neuroplasticity, regional differences in HIV replication or host responses within brain, and blood-brain barrier function.
HIV Neuropathogenesis During Acute and Early Stages of Infection
Identify molecular and cellular mechanisms underlying neurological impairment in acute and early infection in subjects who are not on therapy;
Assess HIV CNS compartmentalization in acute and early stages of infection; and
Evaluate the impact on early initiation of treatment and resulting immune recovery on long term neurologic and neurocognitive outcome, and how factors such as substance abuse affect this relationship.
Viral and Host Genetics
Study the role of viral genetic and epigenetic factors in the pathophysiology of HAND. Understand the role of viral and host transcriptional regulation (including viral protein modifications, histone modifications, changes in chromatin structure, and non-coding RNA) in HIV neuropathogenesis, and the interaction of environmental factors including substance abuse with these regulatory processes;
Conduct viral genetic or host epigenetic studies relating to the establishment and maintenance of CNS latency and reservoirs;
Study the molecular diversity of various HIV-1 genes (e.g., Tat, Nef, Vpr) and resultant functional consequences in the CNS;
Identify the relationships between signaling differences, genetic diversity of HIV proteins and functional effects;
Determine the molecular and genetic mechanisms of HIV clade differences in HIV neuropathogenesis;
Determine the role of host genetic including epigenetic factors in regulating susceptibility to HAND;
Assess the epigenetic host response to viral infection mediated through chromatin modification, non coding RNAs and DNA methylation
Identify host genetic factors regulating responsiveness to anti-retroviral therapy and neuroprotective adjuvant therapies (pharmacogenomics), and the impact of substance abuse or other environmental factors on these relationships;
Delineate the genetic basis of host restriction factors and the maintenance of viral reservoirs in CNS cell types; and
Identify viral and host genetic biomarkers.
Neuroimaging Studies
Use of neuroimaging approaches such as magnetic resonance spectroscopy (MRS), positron emission tomography (PET), magnetic resonance imaging (MRI), functional MRI (fMRI), blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI), diffusion tensor imaging (DTI), arterial spin-labeling MRI (ASL-MRI) and chemical shift imaging to:
Delineate key biological markers that correlate with disease symptoms, progression, and clinically relevant information regarding cognitive, emotional, neurological, and behavioral performance;
Establish relationships between markers identified by neuroimaging and histopathologic markers of neuronal health and inflammation;
Study the role of unique inflammation-related markers identified by neuroimaging in the pathophysiology of HAND; and
Study the impact on the brain of co-occurring HIV infection and exposure to psychoactive agents.
Aging and HAND
Determine the mechanism of HIV neuropathogenesis in older adults;
Assess reciprocal interaction between HIV-associated CNS disease and aging associated neurodegenerative processes as seen in Alzheimer's and Parkinson's Disease; and
Evaluate impact of HAND on biomarkers of aging associated neurodegenerative disease such as amyloid, Abeta42, APOE, tau and phospho-tau.
Therapeutics
Develop antiviral therapeutic drugs capable of penetrating the blood-brain barrier and decreasing the viral load in the CNS;
Research mechanisms of HIV persistence within the CNS and development of strategies or drug therapies to eliminate CNS reservoirs;
Identify adjunctive therapies for the treatment of HAND; including neuroprotective strategies and strategies for reducing CNS inflammation, cellular activation, and neurodegeneration;
Develop therapeutic strategies for increasing the effective concentration, or activity, or entry of HAART and other agents into the CNS;
Ascertain the impact of long term HAART on CNS toxicity;
Design strategies to prevent HAND; and
Assess the impact of substance use on effectiveness, or host/viral responses to combination antiretroviral therapy, or other CNS-specific strategies to prevent or treat HAND.
Animal Models and Specimen Resources
The use of animal models (non-human primates, transgenic mice/rats) is encouraged;
Model systems that address the impact of chronic substance use on neuroinflammatory, neurophysiological, neurocognitive or neurobehavioral consequences of CNS HIV infection would be appropriate; and
The use of human specimen resources from large NIH-funded HIV related studies is also encouraged, including, but not limited to:
○Multi-center AIDS Cohort Study (MACS),
○Women's Interagency HIV Study (WIHS),
○CNS HIV Antiretroviral Therapy Effects Research (CHARTER),
○National NeuroAIDS Tissue Consortium (NNTC).
The NIAAA will consider applications to this Program Announcement that are relevant to the mission of the institute, such as investigations of the co-morbid effects of alcohol use and abuse on mechanisms of HIV infection of the central nervous system.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide. Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-014.html.
EPIDEMIOLOGY AND PREVENTION IN ALCOHOL RESEARCH (R01): PA-11-016
Also note: Epidemiology and Prevention in Alcohol Research (R03): PA-11-017
Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-017.html
Also note: Epidemiology and Prevention in Alcohol Research (R21): PA-11-018
Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-018.html
Components of Participating Organizations
National Institute on Alcohol Abuse and Alcoholism
Application Receipt/Submission Date(s): Multiple dates, see announcement
The National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), encourages the submission of investigator-initiated research grant applications to support research investigating the epidemiology of alcohol use, alcohol-related harms, and alcohol use disorders and the prevention of underage drinking, alcohol-related harms, and alcohol use disorders. Alcohol consumption ranks among the leading risk factors for death and poor health in the United States. Analyses of external, modifiable factors that contribute to death have placed alcohol consumption as the third leading such cause for 2000, after (1) tobacco use, and (2) poor diet and physical inactivity. In 2007, 23,199 deaths in the United States had an alcohol-induced condition as their underlying cause of death, and 45,393 deaths had an alcohol-induced condition as either the underlying cause or a contributing cause of death. The role of alcohol in illness is often inferred from data on health care utilization. A report on alcohol-related hospital discharges based on data from the National Hospital Discharge survey finds that 463,000 hospital discharge episodes in 2007 for persons 15 and older had a principal alcohol-related diagnosis and approximately 1.7 million discharges had an alcohol-related diagnosis of any kind. These overall estimates are surely conservative because they omit a wide range of conditions known to be partially caused by alcohol consumption, including various cancers, cardiac conditions, stroke, gastro-intestinal conditions, and various unintentional and intentional injuries. To fully account for the burden of alcohol-related diseases, some studies attempted to estimate alcohol-attributable fractions for these medical conditions. Taking into account the alcohol-attributable fractions, the CDC's Alcohol-Related Disease Impact (ARDI) system estimates that, on average, about 80,000 deaths each year during 2001-2005 were due to the harmful effect of alcohol consumption. These premature deaths represent about 2.36 million years of potential life lost (YPPLLs).
Epidemiologic research expands knowledge about alcohol use and its associated problems in many ways. It establishes the incidence and prevalence of alcohol use, patterns of drinking (especially high risk drinking), health problems attributable to drinking, and alcohol use disorders. It establishes rates of various problematic consequences of alcohol use such as driving under the influence of alcohol, violent behavior, homicide, suicide, and the spread of infectious diseases such as TB and HIV. Epidemiological studies reveal how these prevalences are distributed among population subgroups potentially elucidating health disparities. They also can indicate the developmental pathways of these phenomena over the life course. Assessment of the causal linkages between alcohol use and health outcomes can reveal both harmful and beneficial effects of alcohol consumption.
Epidemiologic research also identifies risk and protective factors for heavy drinking and alcohol use disorders. The best studies combine risk and protective factors at the individual, familial, small group, and environmental levels. In regard to the environmental level, many interesting contributions have recently been made through spatial modeling studies.
Also important are the relationships between alcohol use disorders, other addictive behaviors, and mental health disorders. Finally, genetic studies are making progress in understanding the interaction between environmental and genetic contributions toward the development of alcohol use disorders.
NIAAA is interested in advancing knowledge in all of the above areas of epidemiologic research.
The key potential benefit of research findings on the rates, developmental patterns, and risk and protective factors of alcohol use and alcohol-related problems is that they will provide a scientific basis for the development of more effective prevention strategies. Indeed an often-neglected task in translational research is making the link between findings of etiological processes and the development and testing of prevention strategies that play on those processes.
Much attention has been given recently to the prevention of underage drinking and on the transition from early drinking to high risk drinking to the development of alcohol use disorders. Many of the prevention initiatives developed in this regard have focused on school-based or college-based strategies for encouraging prevention. Less often examined are interventions that can be implemented in military or workplace settings.
Alcohol consumption during pregnancy has a broad spectrum of deleterious effects on the developing fetus. Effort is needed to develop interventions to prevent fetal alcohol exposure, improve the tools available for diagnosing fetal alcohol spectrum disorders (FASD) more accurately, and broadening our understanding of the mechanisms involved in FASD pathogenesis.
Most commonly, prevention interventions target individually-based mechanisms of change, such as alcohol expectancies or perceived norms about others' drinking. Some studies widen this to include parents, peers, and spouses as agents of change. At wider levels, other programs focus on media messages, alcohol availability, and the complex web of legal and regulatory policy that surrounds the sale and consumption of alcoholic beverages. Especially promising are multi-level strategies that combine both individual and environmental approaches. Also of considerable interest are community-wide strategies that focus a package of several different prevention activities on the same community, hoping to achieve a synergistic effect.
Another promising avenue is to craft prevention strategies effective in specific contexts, such as strategies to engage injury patients seen in emergency rooms, persons screened as high risk drinkers in primary care visits, or pregnant women identified in the course of obstetric or gynecological care. A continuing unresolved need in prevention is to show that preventive strategies known to be effective in the overall population also are appropriate and effective among minority populations. Finally in view of the continuing AIDS epidemic, it is critical to understand the contribution of alcohol use to HIV-related risk taking and to develop strategies that increase early identification of HIV infection and reduce HIV transmission among risk-drinking, alcohol abusing, and alcohol dependent individuals.
In any of these areas, prevention research needs to be concerned with a full range of implementation issues, from demonstrating efficacy in well-controlled trials, to effective delivery under real-world conditions, to the dissemination and translation of effective research into routine practice, and to the demonstration of cost effectiveness and cost offset that can aid in the wider adoption of known-effective strategies. Though most studies focus on establishing the efficacy or effectiveness of one or another intervention strategy, it also is necessary for research to establish better knowledge of the underlying mechanisms of action that promote effectiveness. This task often begins with a careful analysis of the mediators and moderators of successful intervention.
NIAAA wishes to encourage research advances in any of the above areas of prevention science.
Areas of investigation under this Funding Opportunity Announcement (FOA) could include, but are not limited to studies that:
Improve knowledge about the etiology and patterns of comorbidity between alcohol use disorders, other addictive behaviors, and mental health disorders.
Explore factors that influence transitions in drinking patterns across the lifespan, including individual, social context, and environmental factors.
Advance the epidemiology of underage drinking and examine the factors that contribute to early initiation of alcohol use and risk for alcohol use disorders.
Develop innovative statistical methodologies to analyze data sets from cross-sectional and longitudinal studies of alcohol use and develop efficient software tools for implementing these methodologies.
Increase understanding of the role that alcohol plays in the development of chronic diseases and in the management of their treatment.
Improve estimation of alcohol-attributable fractions of morbidity and mortality and the measurement of the burden of alcohol-related illness and mortality.
Improve the targeting of prevention efforts by identifying individuals at highest risk for alcohol use disorders based on family history, genetic association, or biomarker identification.
Replicate and generalize evidence-based environmental strategies developed in successful community trials and undertake studies to develop new community prevention strategies.
Undertake studies of alcohol policies to determine their effects on levels of alcohol-related harms.
Improve understanding of the role of alcohol prices on alcohol consumption and how these effects vary across population groups.
Determine the efficacy and effectiveness of brief interventions among youth to prevent or delay the initiation of alcohol use or to reduce the risk of developing alcohol use disorders and other alcohol-related problems.
Evaluate the effectiveness of brief interventions delivered in a wide variety of contexts, such as emergency rooms, primary care visits, employee assistance programs, and criminal justice settings.
Evaluate strategies to address the problem of college drinking.
Evaluate strategies to reduce alcohol related problems among military personnel and their families.
Develop strategies appropriate for the needs and alcohol-related problems experienced by the elderly.
Develop and test prevention interventions that are based on etiologic findings about the development of alcohol use disorders.
Investigate risk and protective factors for alcohol-related violence and develop and test interventions to prevent alcohol-related violence.
Assess the effectiveness of policies, interventions, and sentencing options designed to reduce drinking driving.
Assess the effectiveness of programs to reduce drinking during pregnancy and the risk of fetal alcohol spectrum disorders (FASD).
Encourage culturally and developmentally appropriate screening, assessment, and intervention, including brief interventions.
Develop and test models using systems science approaches, such as agent-based system dynamics, network, or dynamic micro simulation models, to advance understanding of health-related behaviors and outcomes.
Develop and evaluate effective behavioral, social, and environmental interventions to prevent HIV transmission and acquisition by reducing alcohol-related risk taking.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations, and non-domestic (non-U.S.) entities (foreign organizations). Foreign (non-U.S.) components of U.S. Organizations are allowed. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide. Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-016.html.