Programs and Activities Highlights
- Cryopreservation Workshop Session III: Cryoresearch—Supporting Technology and Resources
The third session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held on September 30, 2024. Session III focused on enhancing the rigor, reproducibility, and applicability of animal research by covering advancements in physical infrastructure, technology, and resources that support cryobiology research. The session also discussed best practices for managing cryopreserved animal models and genetic resources.
- Funding Opportunity for Biomedical Research Facilities
ORIP issued PAR-25-061, Biomedical Research Facilities (C06 Clinical Trial Not Allowed) to invite applications for funding to modernize existing or construct new biomedical research facilities, a reissue of PAR-23-306. Applications from both research-intensive institutions and Institutions of Emerging Excellence in biomedical research from all geographic regions in the nation are strongly encouraged, and each project is expected to produce substantial long-term improvements to the institutional research infrastructure.
- S10 Post-Award Webinar and Panel Discussion
On September 26, 2024, ORIP conducted a webinar for S10 principal investigators (PIs) and institutional signing officials to clarify post-award requirements, share best practices from program officers (POs) and experienced S10 PIs, and provide answers to questions. This inaugural webinar was aimed at enhancing the quality and compliance of S10 reports, ultimately reducing the administrative burden on both PIs and POs. This webinar was well attended, with more than 200 participants.
- NIH Focus Group Meeting on Strategy II of ORIP’s Strategic Plan
In July 2024, ORIP staff members organized and participated in an NIH Focus Group Meeting on Strategy II (Innovative Instruments and Equipment to Accelerate Research Discoveries) of ORIP’s strategic plan. The meeting focused on progress towards Strategy II activities, and ORIP gathered feedback for its next strategic plan. A total of 11 NIH subject matter experts from different institutes, centers, and offices attended the meeting.
- Fourteenth Comparative Medicine Resource Directors Meeting—Breakout Session
The Fourteenth Comparative Medicine Resource Directors (CMRD) meeting was held on August 6–7, 2024. This biennial meeting serves as a pivotal platform for ORIP-supported resource directors to share cutting-edge information, discuss advancements, foster collaborations, and explore future directions for resource management and development in comparative medicine. Centered on the theme of advancing biomedical research through integrative approaches and innovations, the meeting highlighted emerging complementary models, technologies, and methodologies. A breakout session dedicated to instruments allowed participants to discuss strategies for enhancing support for instrumentation and facilities, as well as potential future directions for resource optimization.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- A Humanized Mouse That Mounts Mature Class-Switched, Hypermutated and Neutralizing Antibody Responses
Researchers developed a humanized mouse model (THX, of both sexes) by grafting immunodeficient mice with human CD34+ cells and using 17β-estradiol to promote immune cell differentiation. THX mice reconstitute a functional human immune system, including diverse B- and T-cell populations, and can generate mature antibody responses. They successfully mount neutralizing responses to vaccines, such as the Pfizer-BioNTech COVID-19 vaccine, and can model autoimmune diseases like lupus. This model offers a robust platform for studying human immunity and developing vaccines and therapeutics.
- Fibrin Drives Thromboinflammation and Neuropathology in COVID-19
This study highlights fibrin's pivotal role in the thromboinflammatory and neurological complications associated with COVID-19 and long COVID. Fibrinogen, a key blood clot component, is found abundantly in the lungs and brains of COVID-19 patients, where it binds to the SARS-CoV-2 spike protein. This interaction forms proinflammatory clots that exacerbate systemic inflammation and neuroinflammation, contributing to oxidative stress, macrophage activation, and neuronal damage. Additionally, fibrin suppresses natural killer cells and promotes innate immune activation in both the lungs and brain, even after the infection has resolved. Targeting fibrin’s inflammatory domain with a monoclonal antibody reduces microglial activation, neuronal damage, and thromboinflammation, suggesting potential therapeutic strategies for treating both acute and long COVID symptoms.
- Position-Dependent Function of Human Sequence-Specific Transcription Factors
This study reveals that the position of transcription factor (TF) binding sites relative to transcription start sites (TSSs) significantly influences gene regulation. By analyzing natural genetic variation, TF perturbations, and synthetic regulatory elements, researchers found that many TFs, including activators like NRF1, NFY, and Sp1, can either activate or repress transcription based on their location near the TSS. These findings highlight how the spatial arrangement of TFs governs transcription initiation and explain how DNA sequence variations may contribute to gene expression differences and disease development.
- Non-Human Primate Model of Long-COVID Identifies Immune Associates of Hyperglycemia
This study introduces a nonhuman primate model using SARS-CoV-2-infected African green monkeys (both male and female) to investigate metabolic post-acute sequelae of COVID-19, particularly hyperglycemia. Researchers identified a dysregulated chemokine signature during acute infection that correlates with persistent hyperglycemia up to 4 months post-infection. Despite the lack of long-term viral replication in the liver or pancreas, hyperglycemia was linked to liver glycogen levels. Notably, early administration of the SARS-CoV-2 mRNA vaccine improved glycemic outcomes. This model mirrors human metabolic responses, offering a valuable platform to test therapies for COVID-related metabolic issues.
- High-Resolution In Situ Structures of Mammalian Respiratory Supercomplexes
This study uses in situ cryo-electron microscopy to image porcine mitochondria and reveal the structures of respiratory supercomplexes in their native state. Four main supercomplex organizations (I1III2IV1, I1III2IV2, I2III2IV2, I2III4IV2) were identified, formed by protein–lipid interactions, which influence the geometry of the inner mitochondrial membrane. The study captures reactive intermediates within these supercomplexes, providing insights into the ubiquinone/ubiquinol exchange in complex I and the Q-cycle in complex III. This approach preserves the native environment, offering detailed structural insights into mitochondrial function under physiological conditions.
