Programs and Activities Highlights
- International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project Annual Fall Meeting
The International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project (KOMP) Annual Fall Meeting was held on September 15–16, 2024. An ORIP staff member monitored overall project progress and exchange of scientific knowledge of the international collaboration, contributed to the discussions, conducted an in-depth review of the data provided, and crafted meeting conclusions. The meeting conclusions were communicated to the NIH KOMP Working Group and ORIP and DPCPSI leadership.
- Czech Centre for Phenogenomics Conference 2024
An ORIP staff member represented the International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project at an international community phenotyping conference on September 17–18, 2024. He participated in discussions regarding the use of animal models for the development of preclinical drug testing pipelines, as well as genome editing therapeutics.
- ORIP Concept Clearance (Reissue): National Primate Research Centers Program
In light of the National Primate Research Centers (NPRCs) Program’s demonstrated success and the critical need to ensure national availability of nonhuman primate (NHP) resources, ORIP requested concept clearance from the Council of Councils on September 12, 2024, to continue its support for the program. The NPRCs Program complements and enables the missions of the other NIH institutes and centers by providing the animals, facilities, expertise, and resources required to enable NHP research in specific disease areas.
- Cryopreservation Workshop Session II: Cryopreservation and Development of Sustainable Germplasm Repositories for Aquatic Biomedical Models
The second session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held on September 9–10, 2024. Session II focused on the advancements and future needs of genetic resources of aquatic biomedical models, including zebrafish, Xenopus, Ambystoma, and Xiphophorus. The meeting featured three keynote talks and panel presentations by more than 36 panelists. The workshop participants discussed challenges associated with funding and training, the need for standardized protocols, and the benefits that universal data management systems and training hubs would provide.
- PAR-24-258: Research Resource for Human Organs and Tissues (U42 Clinical Trial Not Allowed)
The purpose of this funding opportunity is to support a Human Tissue and Organ Research Resource program to enable the continued availability of human tissues and organs to biomedical researchers. The overall goal of the research resource is to provide a wide variety of human tissues and organs, both diseased and non-diseased, to investigators. The research resource is expected to facilitate the procurement and preservation of human tissues and organs, as well as the distribution of these materials to qualified biomedical researchers.
Read more in the archive.
ORIP-Supported Research Highlights
- A New Atlas to Study Embryonic Cell Types in Xenopus
Petrova et al. developed a new single-cell atlas for developmental stages in Xenopus that encompasses gastrulation, neurulation, and early tailbud. Compared to its predecessors, the new atlas enhances gene mapping, read counts, and gene/cell type nomenclature. It leverages the latest Xenopus tropicalis genome version to maintain consistency with previous cell type annotations while rectifying prior nomenclature issues. The new resource also emphasizes previously unexplored germ cell populations in which novel transcription onset features have been uncovered. Finally, the new atlas offers interactive exploration through a user-friendly web portal and allows users to download complete data sets, as well.
- Dual Blockade of IL-10 and PD-1 Leads to Control of SIV Viral Rebound Following Analytical Treatment Interruption
Pereira Ribeiro et al. tested a hypothesis that blockading two immune molecules, IL-10 and PD-1, following treatment interruption could help control viral rebound in antiretroviral therapy (ART)–treated rhesus macaques of both sexes infected with simian immunodeficiency virus (SIV). When measured at 24 weeks following treatment interruption, durable control of viral rebound was seen in 9 out of 10 combo-treated macaques. The investigators also found they could predict control of viral rebound based on induction of inflammatory cytokines, proliferation of effector CD8+ T cells, and reduced expression of BCL-2 in CD4+ T cells prior to treatment interruption. These results could provide a way to achieve long-lasting control of HIV infection after discontinuing ART.
- Commentary: The International Mouse Phenotyping Consortium: High-Throughput In Vivo Functional Annotation of the Mammalian Genome
The International Mouse Phenotyping Consortium (IMPC), a collectively governed consortium of 21 academic research institutions across 15 countries on 5 continents, represents a groundbreaking approach in genetics and biomedical research. Its goal is to create a comprehensive catalog of mammalian gene function that is freely available and equally accessible to the global research community. So far, it has uncovered the function of thousands of genes about which little was previously known. By 2027, when the current round of funding expires, the IMPC will have produced and phenotyped nearly 12,000 knockout mouse lines representing approximately 60% of the human orthologous genome in the mouse. This new knowledge has produced numerous insights into the role of genes in health and disease, including informing the genetic basis of rare diseases and positing gene product influences on common diseases.
- The Effect of Common Paralytic Agents Used for Fluorescence Imaging on Redox Tone and ATP Levels in Caenorhabditis elegans
Caenorhabditis elegans is a highly valuable model organism in biological research. However, these worms must be paralyzed for most imaging applications, and the effect that common chemical anesthetics may have on the parameters measured, especially biochemical measurements, such as cellular energetics and redox tone, is poorly understood. In this study, the authors used two reporters—QUEEN-2m for relative ATP levels and reduction-oxidation sensitive GFP for redox tone—to assess the impact of commonly used chemical paralytics. The results show that all chemical anesthetics, at doses required for full paralysis, alter redox tone and/or ATP levels and that anesthetic use alters the detected outcome of rotenone exposure on relative ATP levels and redox tone. Therefore, it is important to tailor the use of anesthetics to different endpoints and experimental questions and to develop less disruptive paralytic methods for optimal imaging of dynamic in vivo reporters.
- Spatiotemporal Image Reconstruction to Enable High-Frame-Rate Dynamic Photoacoustic Tomography With Rotating-Gantry Volumetric Imagers
Dynamic photoacoustic computed tomography (PACT) is a valuable imaging technique for monitoring physiological processes. However, the current imaging techniques are often limited to 2D spatial imaging. While PACT imagers capable of taking 3D spatial images are commercially available, these systems have substantial limitations. Typically, the data are acquired sequentially rather than simultaneously at all views. Because the objects being imaged are dynamic and can vary during this process, image reconstruction is inherently difficult, and the result is often incomplete. Cam et al. propose an image reconstruction method that can address these challenges and enable volumetric dynamic PACT imaging using existing preclinical imagers, which has the potential to significantly advance preclinical research and facilitate the monitoring of critical physiological biomarkers.
Read more in the archive.
