Highlighting Progress Archives

ORIP Theme I - Strategy 1

ORIP Participates in Rapid Zika Virus Model Development

February 28, 2017

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.

ORIP Theme I - Strategy 2

A Mutant Mouse Centralized Repository for Researchers

June 15, 2017

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

A Four Dimensional Atlas of Dynamic Embryo Imaging

June 15, 2017

The complexity of the neurological circuitry and development in higher ordered vertebrates has hindered the ability to dynamically capture single cells, the entire nervous system, and the overall process of development. The invertebrate nematode (roundworm) Caenorhabditis elegans (C. elegans) is an ideal organism for modeling neurodevelopment because of its simplistic nervous system. C. elegans is used to answer important research questions regarding how cells function and the role of certain genes. Scientists have grappled with modeling embryo development in this organism because of rapid embryonic movement, muscle twitching, and the lack of spatial resolution commonly observed by microscopy. These challenges result in poor image quality and lowered dimensionality. Despite certain technical enhancements in microscopic imaging, the morphological changes in the embryo hamper the ability to view individual cells. Genetically engineered C. elegans that express fluorescent markers are being used to easily view individual cells and dynamically track the stages of development. The National Institutes of Health supported a research collaboration to create a novel four dimensional (4D) atlas of embryogenesis and neurodevelopment in C. elegans1 through a project called Worm Global Understanding in Dynamic Embryonic Systems (WormGUIDES).2 This atlas is the first 4D embryo atlas of nuclear positions of all cells of the worm embryo. Captured images representing the entire organism can be computationally “untwisted.”1 Collected images allow scientists to track cellular components and to combine data from multiple C. elegans to model time-lapse development. Available through a mobile or desktop application3, WormGUIDES develops an interactive tool that presents the 4D atlas of single cells and their coordinated movement, gene expression, and overall development. Users can access information regarding cellular positioning and neuron growth during embryogenesis. WormGUIDES provides a reference tool and may assist in identifying therapeutic targets of disease.

 

References

1 Christensen RP, Bokinsky A, Santella A, Wu Y, Marquina-Solis J, Guo M, Kovacevic I, Kumar A, Winter PW, Tashakkori N, McCreedy E, Liu H, McAuliffe M, Mohler W, Colón-Ramos DA, Boa Z, Shroff H. Untwisting the Caenorhabditis elegans embryo. eLife. 2015(4):e10070

2 Santella A, Catena R, Kovacevic I, Shah P, Yu Z, Marquina-Solis J, Kumar A, Wu Y, Schaff J, Colón-Ramos, DA, Shroff H, Mohler WA, Bao Z. WormGUIDES: an interactive single cell developmental atlas and tool for collaborative multidimensional data exploration. BMC Bioinformatics. 2015 June 9(16):189.  

3 http://www.wormguides.org/home

Pilot Centers for Precision Modeling

February 28, 2017

Recent scientific and technological advances, such as affordable whole genome sequencing and molecular profiling, enable us to study the genetics and pathogenesis of many human diseases. The goal of using this information is to provide patient-precise treatments based on their unique genetic composition and molecular phenotype. Obstacles to this goal are the absence of an effective means to interpret patient genetic/omic data for clinical use in diverse patient populations. Creating animal models to generate reliable preclinical data for human studies is a fundamental step needed to reach the goal.

In response, the ORIP Division of Comparative Medicine initiated the Pilot Centers for Precision Disease Modeling program to provide advanced animal models to the biomedical community for: 1) examining the causal relationships of genetics and omic information to human biology and disease; 2) validating disease-associated genetic variations and biomarkers; 3) reducing drug candidate attrition; and 4) developing new individualized therapies for monogenic and complex disorders. These Centers are creating pipelines for pre-clinical scientific discovery, disease modeling, and development of interventions based on innovative animal models. Eventually these preclinical pipelines may play an integral role in patient diagnostics, care and therapeutic treatment.

ORIP Theme I - Strategy 3

A Mutant Mouse Centralized Repository for Researchers

June 15, 2017

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

ORIP Theme II - Strategy 1

Implement Improved metrics to evaluate the S10 Program

March 30, 2017

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.

ORIP Theme II - Strategy 2

Provide Support for Technologies

March 30, 2017

In fiscal year (FY) 2016, the S10 Shared/High-End Instrumentation Program funded 107 awards. As in the past, the Program responded to the needs of researchers from across the nation by funding different types of instruments proportionally to requests received and covering a broad range of technologies; including, X-ray detectors, mass and NMR spectrometers, atomic force, light and electron microscopes, calorimeters, sequencers, biomedical imagers, computers and data storage systems. The Program responds to the emerging needs of the researchers as new technologies become available and enter the market; this year the Program awarded a 3D printer, which is used to create specialized nozzles for X-ray free electron laser imaging of molecular assembly structures.

Collectively, instruments awarded in FY 2016 will immediately benefit the research of almost 2000 investigators supported by grants from all NIH Institutes and Centers, several other Federal agencies including NSF, DOD, DOE, NASA, DARPA, over 80 private foundations, and start-up funds for new faculty at academic institutions.

Partner with NIH ICs

As part of an NIH-wide focus, ORIP is interested in best practices for data generation, management and sharing. ORIP, NIGMSNLM, and BD2K, collaborated to issue the notice (NOT-OD-16-091) requesting information on Data Annotation in Biomedical Core Research Facilities and Related Needs for Community Education and Training. (See the Executive Summary of results).