Programs and Activities Highlights
- Reissue ORIP Concept Clearance: Shared Instrumentation Program
ORIP presented this concept clearance for reissue at the January 2024 NIH Council of Councils meeting. The initiative supports purchases of state-of-the-art, commercially available instruments to NIH-funded investigators. The program is based on shared use, which makes it cost efficient and beneficial to thousands of investigators in hundreds of institutions nationwide.
- Oklahoma Medical Research Foundation Site Visit
ORIP program staff conducted a virtual final site visit to the Oklahoma Medical Research Foundation (ORMF) on March 18, 2024, to conclude the 20-year oversight period of grants C06RR014570, C06RR017446, and C06RR030593. These three awards provided funding to significantly renovate existing spaces and construct new spaces that have facilitated OMRF’s research on rheumatology, sarcoidosis, and autoimmune disorders like lupus and rheumatoid arthritis. ORMF reported that the funded facilities added significant funds in sponsored research and helped fund two new research centers. Additionally, OMRF scientists co-founded four companies, two of which have reached commercialization of their new technologies.
- Limited Competition: Development and Renovation of Facilities for Expanding the Breeding Capacity of Specific Pathogen Free Non-Human Primates to Support HIV/AIDS–Related Research (C06 Clinical Trial Not Allowed)
Nonhuman primates (NHPs) serve as a critical animal model for biomedical research, including HIV-related research. The COVID-19 pandemic and export bans from Asian countries exacerbated the existing NHP shortage. Despite NIH efforts to improve NHP availability, limited facility resources still hamper the safe and effective production of this animal model. To meet this urgent need, ORIP, in collaboration with the Office of AIDS Research, published a new notice of funding opportunity titled Development and Renovation of Facilities for Expanding the Breeding Capacity of Specific Pathogen Free Non-Human Primates to Support HIV/AIDS–Related Research. This funding opportunity is expected to expand the support of NHP breeding resources and increase the output of NHP models substantively and cost-effectively, addressing the urgent need of NHPs for HIV research.
- Site Visit to the Gladstone Institute
ORIP staff conducted a virtual site visit on November 13, 2023, to evaluate the progress of a construction award (C06RR018928) to the Gladstone Institute. This grant provided funding for the fit-out of animal facilities in the new laboratory building at the University of California, San Francisco, Mission Bay campus to support research on cardiovascular, neurological, viral, and immune diseases. The facility has supported 30 laboratories for animal studies since 2003 and enabled research funded by more than $145 million in NIH grants. Gladstone includes more than 500 researchers, including 2 Nobel laureates, and 80% of the faculty have benefitted from the animal facility. Gladstone has produced about 300 issued U.S. and foreign patents; one-third of these patents relate to animal models.
- Pre-Application Webinar for Non-Human Primate Facilities (PAR-24-033) and Biomedical Research Facilities (PAR-23-306)
ORIP held a pre-application webinar in December 2023 for two notices of funding opportunities: Development and Renovation of Facilities for Expanding the Breeding Capacity of Specific Pathogen Free Non-Human Primates to Support HIV/AIDS-related Research (C06 Clinical Trial Not Allowed) and Biomedical Research Facilities (C06 Clinical Trial Not Allowed). ORIP program staff presented a program overview; explained the goals and application structures of these funding opportunities to around 130 attendees; and answered questions regarding budget, timeline, and review. Follow-up questions sent by email also were answered by ORIP program staff.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- Long COVID-19 Manifests With T Cell Dysregulation, Inflammation and an Uncoordinated Adaptive Immune Response to SARS-CoV-2
Researchers analyzed blood samples from male and female individuals with long COVID-19 and control trajectories 8 months post-SARS-CoV-2 infection. Long COVID-19 patients displayed systemic inflammation, immune dysregulation, and altered T‑cell subset distribution. They exhibited increased frequencies of CD4+ T cells poised for tissue migration, exhausted SARS-CoV-2-specific CD8+ T cells, and disrupted coordination between T- and B-cell responses. Findings suggest improper immune crosstalk in long COVID-19, contributing to symptoms. This study sheds light on pathophysiology, potentially informing therapeutic strategies and improving patient outcomes in managing this debilitating condition.
- Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
This study presents a key mechanism that prevents pancreatic ductal adenocarcinoma (PDAC) from undergoing neoangiogenesis, which affects its development, pathophysiology, metabolism, and treatment response. Using human and murine PDAC explants (sex unknown), which effectively retain the complex cellular interactions of native tumor tissues, and single-cell regulatory network analysis, the study identified a cascade of three paracrine pathways as a key suppressor of angiogenesis in KRAS-mutant PDAC cells. This study provides an experimental paradigm for dissecting higher-order cellular interactions in tissues and has implications for PDAC treatment strategies.
- Motile Living Biobots Self-Construct From Adult Human Somatic Progenitor Seed Cells
Anthrobots, spheroid-shaped biological robots derived from adult human lung cells (sex unknown), self-construct into multicellular biobots with cilia-powered locomotion. They exhibit diverse behaviors and morphologies, influenced by microenvironmental cues, without genetic editing. Anthrobots can repair scratches in human neural cell sheets, suggesting biomedical potential. This study illuminates plasticity in adult somatic cells and the potential for diverse body shapes and behaviors in living constructs. Anthrobots offer a novel platform for studying morphogenetic processes and discovering structures with biomedical relevance.
- Obesity Causes Mitochondrial Fragmentation and Dysfunction in White Adipocytes due to RalA Activation
High-fat diet (HFD) induces mitochondrial fragmentation in white adipocytes via increased expression and activity of the small GTPase RalA. This fragmentation reduces oxidative capacity and promotes weight gain. Targeted deletion of RalA prevents fragmentation, enhances fatty acid oxidation, and reduces HFD-induced weight gain in mice. Mechanistically, RalA promotes mitochondrial fission by dephosphorylating Drp1. Adipose tissue expression of human Drp1 homolog, DNM1L, correlates with obesity and insulin resistance. Chronic RalA activation suppresses energy expenditure by promoting excessive mitochondrial fission, contributing to metabolic dysfunction in obesity.
- Epigenetic Dysregulation From Chromosomal Transit in Micronuclei
The authors reported a mechanistic link between epigenetic alterations and chromosomal instability induced during their transit in micronuclei, both being hallmarks of advanced and metastatic cancers. It was demonstrated that the landscape of histone post-translational modifications was profoundly changed due to missegregation of mitotic chromosomes, their sequestration in micronuclei, and subsequent rupture of the micronuclear envelope. The transcriptional redistribution was attributed to micronuclei’s strong positional bias with increased promoter accessibility. The continuous formation and reincorporation of micronuclei promotes epigenetic reprogramming and heterogeneity in cancer.
Read more in the archive.
