Strategic Plan

Office of Research Infrastructure Programs (ORIP) Strategic PlanThe Cover of the Strategic Plan Document

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The National Institutes of Health (NIH) established the Office of Research Infrastructure Programs (ORIP) in December 2011 when the appropriations bill for Fiscal Year 2012 was passed by Congress and signed into law. ORIP provides research infrastructure and related research programs. ORIP is located in the NIH Office of the Director’s (OD) Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), which identifies and enhances trans-NIH research in critical areas of emerging scientific opportunities and reports on knowledge gaps that merit further research through its scientific offices. The trans-NIH nature of ORIP activities demands close collaborations between ORIP divisions (DCM, DCI), DPCPSI offices, and the entire NIH to optimize support of all disease areas and across the basic, translational, and clinical research continuum.

ORIP’s 2016–2020 Strategic Plan provides the tools needed to forge successful partnerships with NIH ICs, funding agencies, and the scientific community to support the goals of the NIH mission. This 5-year plan presents three thematic areas that were identified during an 18-month planning process. NIH grantees, NIH leadership and colleagues, NIH Council of Councils members, and the general public provided valuable input. The strategic themes define the overall vision, while the outlined strategic goals are ORIP’s focus areas. The objective of ORIP’s Strategic Plan is not only to build on its significant past investment and existing activities, but also to add new ideas and perspectives to emerging research. Many of the outlined areas build on current programs that have benefited from ORIP’s past support. Other areas involve judicious expansion of existing programs and new directions identified as targets for future growth.

The ORIP Strategic Plan research infrastructure high priority thematic areas are:

  1. Developing models of human diseases.
  2. Accelerating research discoveries by providing accessto state-of-the-art instrumentation.
  3. Training and diversifying the biomedical workforce.

ORIP Theme I

Developing Models of Human Diseases

Scientists use nonhuman models of human diseases when they are trying to learn about basic disease mechanisms and therapies from experiments that could not be conducted in humans. Evolving technologies and tools for genetic modification will allow currently used animal models to be complemented by new models that will be more focused and predictive of the actual human disease. Even with this new precision, no single animal model will ever recapitulate human disease with complete fidelity. This fact is becoming ever more apparent as we learn about the complexity of human physiology and pathology using the same molecular tools that have allowed us to build better animal models. These new tools and technologies enable scientists to probe deeper into the molecular origins of the clinical symptoms (phenotypes) observable in human diseases. To study, understand, and eventually cure complex diseases in humans will require the use of multiple extensively phenotyped models that mimic the different pathogenic events leading to the disease. Using complementary models may provide the highest predictive capacities, but it will also require new and more in-depth knowledge of disease processes in both models and humans. Additionally, functional alignment of models will require new efforts to integrate data and map phenotypes across model species and into humans. Coupled with a careful choice from among different model systems, this approach should lead to an increased level of predictive power, a decrease in new drug attrition rates, and an increase in the efficacy of new treatments.

Strategy 1 - Expand and ensure access to animal models.

ORIP's disease models program supports the development of new and improved animal models that complement those traditionally used to study human diseases. In addition to the generation of new model systems, it is equally important to ensure that animal models are all readily available for distribution in research studies today, as well as preserved for use by future scientists.

The number and complexity of disease models—naturally occurring, induced, and genetically engineered—are increasing much faster than our ability to effectively access and use the new information to speed life-saving therapies to the clinic. A critical need exists for the creation of innovative knowledge generation and retrieval systems to give translational researchers the ability to analyze the full spectrum of clinically relevant model systems (animal models, cell and organ cultures, tissue and organ chips, and computational methods) and select the most appropriate models for their research. To facilitate the development and ensure the availability of critical animal models, ORIP will:

  • Continually evaluate the utility of and provide sustained support for valued traditional and nontraditional animal models.
  • Evaluate and promote the application of new technologies to improve generation, preservation, and distribution of rodent, nonhuman primate (NHP), aquatic, and other models.
  • Partner with NIH ICs to create information retrieval platforms, knowledge systems, and data repositories to assist scientists in the selection and use of models of human disease.

Highlighting Progress: ORIP Participates in Rapid Zika Virus Model Development

Zika virus (ZIKV) is an emerging mosquito-borne virus that was first detected in Brazil in 2015 and has since become a global pandemic. The World Health Association declared the ZIKV pandemic a public health emergency in February 2016. Because there is little known to date about the virus, there is an urgent need for animal models to better understand the pathology of transmission and to test therapeutic interventions.

ORIP has a particular interest in developing and characterizing animal models that can be used to study basic aspects of ZIKV infection and pathogenesis and has responded to the global ZIKV pandemic. ORIP has awarded several grants following their notice to participate in the funding opportunity announcement (FOA) “Rapid Assessment of Zika Virus (ZIKV) Complications (PAR-16-106).” This FOA promotes ongoing submission, review, and award of applications that address issues related to this emerging pathogen as a public health crisis. ORIP meets with the other 8 participating Institutes and Centers (NICHD, NIAID, NIDCR, NINDS, NEI, NIBIB, NIMH and NHLBI) to discuss best practices and implementation of continuous submission of applications.

Strategy 2 - Continue to develop and enhance human disease models and research-related resource programs to advance medical research.

Today’s biomedical researchers have a wide variety of model systems from which to choose when studying human biology and disease states. Therapeutic approaches can be tested for effectiveness in animal models prior to their introduction into human clinical trials. The advent of new technologies that permit the construction of a mouse with a human immune system has resulted in opportunities to further develop model systems that are more precise and predictive of human pathologies. To ensure that disease models co-evolve with technologies, knowledge of human biology, and the needs of the research community, ORIP will:

  • Identify opportunities and challenges for animal models to become precise and predictive models of human pathologies.
  • Promote phenotyping and annotation of human disease model systems.

Highlighting Progress: Regulation of Tissue Expansion in Drosophila Intestine

Scientists at Indiana University are delineating the molecular and cellular activities of the conserved regenerative pathway, Lin-28, that is involved in developmental timing and regulates the self-renewal of stem cells.  Essential details about this pathway, its mRNA targets, mechanism of action and regulation are currently unknown. In a recent study, scientists reported that fragile X mental retardation protein (FMRP) functions via LIN-28 to control the behavior of intestine progenitor cells in response to nutrition. Since the loss of FMRP in humans causes fragile X syndrome (FXS), the study raises the possibility that defective adaptive growth might be causing pathological conditions that are affecting FXS patients.

Highlighting Progress: Hypothalamic Production of Estradiol is Essential for Induction of the Luteinizing Hormone (LH) Surge and Ovulation in Nonhuman Primates (NHPs)

Exogenous estradiol treatment cannot elicit an LH surge in ovariectomized NHPs whose endogenous estradiol is suppressed with an aromatase inhibitor. These results indicate the obligatory role of hypothalamic estradiol production in stimulating the LH surge and subsequent ovulation.

Highlighting Progress: Inhibition of tryptophan Catabolism Augments Immune-mediated Control of Mycobacterium tuberculosis (Mtb)

Tryptophan metabolites suppress host immunity and Mtb induces expression of indoleamine 2,3-dioxygenase (IDO) enzyme, which is involved in tryptophan catabolism. Suppression of the IDO enzyme in Mtb-infected macaques reduced bacterial burden, pathology, and clinical signs of tuberculous (TB) suggesting inhibition of IDO has potential for an effective and clinically relevant host-directed therapy for TB.

Strategy 3 - Explore ways to improve the reproducibility of research using disease models.

Reproducible research is essential for scientific progress. Preclinical investigations are particularly susceptible to reproducibility issues, as many factors are experimentally manipulated to understand the biological system under study. Examples include experimental design factors, such as environmental (diet, temperature) and biological qualities (genetic background, sex), that can affect the reproducibility of animal- and cell-based disease models. To enhance the reproducibility of biomedical research, ORIP will:

  • Develop research resources to train investigators on protocols that influence reproducibility and validation of models of human diseases.
  • Explore the use of online learning and the Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) programs to promote training in reproducibility.
  • Foster relationships between intramural and extramural groups with expertise in improving the rigor of research using animal models.
  • Make strategic investments into infrastructure tools to enhance the reproducibility of specific disease models.

Highlighting Progress: A Mutant Mouse Centralized Repository for Researchers

The Mutant Mouse Resource and Research Center (MMRRC) is a program of the National Institutes of Health (NIH) that strives to expand and ensure access to well-defined, high-quality rodent models for biomedical research. Supported by ORIP’s Division of Comparative Medicine and aligned with ORIP’s 2016‒2020 Strategic Plan to develop novel models of human diseases to study, understand, and eventually cure complex diseases, the MMRRC consists of four centers (at the University of California at Davis, University of Missouri, University of North Carolina at Chapel Hill, and The Jackson Laboratory) that operate as a central repository to accept, cryopreserve, maintain, and distribute mutant mouse strains. By accepting reagents from researchers, the MMRRC promotes an environment of responsible conduct of research, where scientists are obliged to share their resources with each other, which minimizes costs and time associated with the distribution of reagents. From 2010 to April 2017, the MMRRC received more than 8,633 orders from investigators. The MMRRC saves scientists time and costly efforts of having to house, breed, rederive, and characterize mice and conduct duplicative studies due to unexpected phenotypes and experimental variability. The MMRRC now offers next-generation gene sequencing technology of gut microbiota in mice to better equip researchers to conduct reliable and reproducible science, and to avoid unexpected study results. In 2016, the NIH funded the second phase of the newly developed Common Fund’s Knockout Mouse Project (KOMP 2) to make more than 3,000 new genetic knockout mice available through the MMRRC program

Strategy 4 - Support the modernization and improvements of animal research facilities to enhance animal maintenance and care.

Biomedical researchers require high-quality, disease-free animals and specialized animal research facilities. ORIP’s Animal Facility Improvement Program (AFIP) provides funds to institutions to modernize animal research facilities through alterations and renovations and to purchase equipment for animal resource centers. To ensure modernization and improvement of animal research facilities, ORIP will:

  • Continue to support the AFIP in collaboration with NIH ICs and other Federal agencies.
  • Provide support for specialized animal facilities, such as a gnotobiotic facility or surgical suite, to meet the emerging research needs of NIH-supported investigators.
  • Solicit applications for SBIR/STTR to bring new animal care technologies to biomedical research.


Accelerating Research Discoveries by Providing Access to State-of-the-Art Instrumentation

The two categories of ORIP’s S10 program, the Shared Instrumentation Grant (SIG) and the High-End Instrumentation (HEI) programs, are unique at the NIH, as they support purchases of commercially available instruments to enhance the research of NIH-funded investigators. Without access to appropriate modern tools and equipment, it is impossible to conduct pioneering research, to bring forward basic science discoveries, or to design the translational implementation of these studies. The S10 program provides funding for expensive shared instruments which otherwise would not be available to many researchers. The program funds a broad spectrum of technologies that are used in all areas of biomedical research, from fundamental scientific investigations in biophysics and biochemistry to implementation of novel medical procedures and treatments. Every instrument awarded by the S10 program is used on a shared basis, so that thousands of investigators in hundreds of research institutions nationwide have benefited over the years. ORIP will maintain the vitality of the S10 program and the essential role it plays in supporting the NIH research community and advancing the forefront of biomedical research.

Strategy 1 - Optimize the instrumentation program through forward-looking program management.

Over the years, the demand for different technologies has changed, both as new tools have become available and as the particular focus of scientific efforts has shifted. It is necessary that the instrumentation program remains responsive to these evolving needs of the community. To ensure that ORIP’s S10 program continues its broad reach and important benefits, ORIP will:

  • Implement improved metrics to evaluate the S10 program.
  • Modify the S10 program requirements and administration to augment its costeffectiveness and utility for the biomedical research community.
  • Update program guidelines to serve the needs of all of the S10 program users (both SIG and HEI).

Highlighting Progress: Implement Improved metrics to evaluate the S10 Program

From the currently submitted applications, ORIP staff drew information about the status of the instruments awarded to the applicant institutions in the last 5 years; that is, fiscal years (FYs) 2011-2015. ORIP’s analysis covered over 80% of all instruments awarded in that period; these instruments are well maintained and being used. Based on the data provided, more clearly defined instructions for responding to questions on instrument status and hours of use were included in funding announcements for FY 2017.

Modify the S10 program requirements and administration to augment its cost effectiveness and utility for the biomedical research community.

In FY 2016, ORIP introduced an opportunity to apply for Special Use Instruments. These instruments can be used in a clinical setting as long as special budgetary and managerial conditions are met to ensure the priority and predominant protected time for biomedical research. One such award was issued for a system consisting of a 3 Tesla MRI scanner and an X-ray angiography interventional system to support research and clinical uses.

Strategy 2 - Continue to accelerate research discoveries by providing access to state-of-the-art instrumentation.

ORIP’s S10 program has served the extramural NIH research community well for more than 25 years. Instruments funded by the S10 program enable work conducted by all NIH ICs at hundreds of research institutions nationwide. The importance of the S10 program for advancing basic science discoveries and their translational implementation is well recognized by the biomedical research community. To continue this record of accelerating research discoveries, ORIP will:

  • Provide support for technologies needed by the biomedical research community.
  • Partner with NIH ICs to leverage resources and extend the reach of the S10 program.

Highlighting Progress: Targeting Neoplastic Pericytes to Improve Treatment of Brain Tumors

A major obstacle for drug delivery to malignant brain tumors is the existence of a Blood Tumor Barrier (BTB).  Scientists at the Cleveland Clinic discovered that glioma stem cell (GSC)-derived pericyte coverage of tumor vasculature is inversely correlated with glioblastoma patient survival after chemotherapy. Using a PerkinElmer IVIS Spectrum CT (S10OD18205), one of 9 small-animal multi-modality CT imagers funded by the ORIP Shared Instrumentation Program in the last 3 years, researchers demonstrated that targeting the GSC-derived pericytes disrupts the BTB, and enhances the chemotherapeutic efficacy. Targeting neoplastic pericytes to significantly improve treatment of brain tumors may hold promise.

Highlighting Progress: Novel Agent for Redox-Activated Photoacoustic Imaging-Guided Photothermal Cancer Therapy

Scientists at the University of Wisconsin designed an ultra-small molybdenum-based cluster agent with long in-vivo-circulation half-life for photoacoustic (PA) image-guided photothermal therapy. Accumulating in the tumor, these clusters self-assemble into larger nanoclusters which absorb near-infrared light. Using an ultrasonic and photoacoustic imaging system (S10OD18505) that serves 13 major projects and was funded by the ORIP Shared Instrumentation Program, investigators demonstrated efficacy of these clusters for PA image-guided tumor ablation in-vivo. These findings may establish a new paradigm for PA imaging agents, an approach that bridges the conventional concepts of "molecule" and "nano" in the bioimaging field.

Highlighting Progress: Delineation of Brain Activity at the Columnar Level by fMRI

The fMRI blood oxygenation level-dependent (BOLD) signal has specificity to detect brain activity at the columnar level. Using a 9.4T MRI system (S10 RR017799), that is shared among 12 users and was funded by the Shared Instrumentation Grant Program, researchers at Vanderbilt University demonstrated that BOLD signal is aligned spatially with the local field potential signals from multi-channel in-situ electrode array. Such arrays are considered a gold standard to measure brain activity. This work shows that the intrinsic resolution of the brain-activation signal detected by the high-field fMRI BOLD method approaches the spatial precision of invasive multi-electrode electrophysiology.


Training and Diversifying the Biomedical Workforce

The most important ingredient in biomedical science is the inquisitive mind of the well-trained scientist. Maintaining this “human infrastructure” requires careful investments, in both time and money, to ensure that the next generation of biomedical researchers reaches its full potential. To continue the advancement of human health, the NIH must attract some of the best minds from the full diversity of each generation into medical research. ORIP will support activities designed to complement other NIH programs, to improve scientific training, and to advance a diverse research workforce.

Strategy 1 - Train veterinary scientists as translational researchers.

Veterinary scientists, biomedical scientists with a veterinary degree, can offer a distinct perspective and expertise to translational biomedical research through their comparative understanding of disease models. Veterinary scientists can make unique recommendations regarding the development, refinement, and reproducibility of disease models and optimize laboratory animal maintenance and care. However, because hurdles continue to impede the entry of veterinarians into basic and applied research careers, ORIP will:

  • Identify and address challenges and opportunities for veterinary scientists to acquire the skills needed to participate in biomedical research.
  • Collaborate with NIH ICs to develop programs that capitalize on the specialized expertise of veterinary scientists (e.g., pathology, emerging infectious diseases, and epidemiology).
  • Promote biomedical research collaborations between physicians and veterinary scientists.
  • Train veterinary scientists to lead activities that integrate biomedical findings across model species (e.g., multidisciplinary training programs).
  • Support dual-degree training programs for veterinary scientists.

Learn more about the Mission Statement and Activities.