Programs and Activities Highlights
- 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.
- 22nd Annual Meeting of the Mutant Mouse Resource and Research Center Consortium
ORIP participated in organizing and presented at the annual Mutant Mouse Resource and Research Center (MMRRC) Consortium meeting, which was held on August 7–8, 2024. This hybrid meeting took place in Bethesda, Maryland, and was attended by the MMRRC principal investigators and co-investigators, invited speakers, members of the advisory board, and ORIP staff and leadership. Sessions were organized on the following topics: data management and precision model systems, topic discussions, center updates, and external advisory committee discussion.
- Nonhuman Primate Evaluation and Analysis
On August 15, 2024, NIH released a report prepared by ORIP and the Office of AIDS Research on the evaluation and analysis of nonhuman primate (NHP) supply and demand in U.S. biomedical research, spanning research fields, species, services, and future needs. The purpose of the report is to improve our understanding of the demand for and supply of NHPs within the United States, with particular emphasis on the resources supported by NIH. The report identifies a trend of increasing demand for NHPs in several critical areas of NIH-funded research and highlights challenges, such as balancing demands with breeding efforts that could be met through collaborative efforts across NIH and between NIH and other federal agencies. NIH previously conducted a similar analysis, prepared by ORIP and released in September 2018, on which this report builds. The findings from the report will inform NIH strategies to benefit the greater biomedical research community.
- Cryopreservation Workshop Session I: Cryopreservation and Other Preservation of Invertebrate Models in Biomedical Research
The opening session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held on September 6, 2024. This session focused on cryopreservation and other alternative long-term preservation methods for invertebrate models widely used in biomedical research. Presentations covered current techniques, limitations in preserving these organisms, and key insights gained from preserving other invertebrate species. Participants highlighted critical gaps and challenges in the field, fostering discussion on advancing preservation strategies.
Read more in the archive.
ORIP-Supported Research Highlights
- 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.
- Gap-Junction-Mediated Bioelectric Signaling Required for Slow Muscle Development and Function in Zebrafish
Using the neuromuscular system of embryonic zebrafish as a model, Lukowicz-Bedford et al. have identified a protein responsible for controlling bioelectric signaling in slow muscle development and function. Bioelectric signaling is a form of intercellular communication that has emerged as a key regulator of animal development. These signals can be mediated by gap junction channels—fast, direct pathways between cells for the movement of ions and other small molecules—which are formed in vertebrates by a highly conserved transmembrane protein family called connexins. However, the connexin gene family is large and complex, making it challenging to identify specific connexins that create channels within developing and mature tissues. This work reveals a molecular basis for gap junction communication among developing muscle cells and reveals how disruptions to bioelectric signaling in the neuromuscular system may contribute to developmental myopathies.
- Immunization With Germ Line–Targeting SOSIP Trimers Elicits Broadly Neutralizing Antibody Precursors in Infant Macaques
Broadly neutralizing antibodies (bnAbs) offer a promising approach for preventing and treating HIV infection, but the ability to induce bnAbs at protective levels has been a challenge. Previous studies have shown that children living with HIV develop bnAbs more efficiently than adults living with HIV. This study evaluated the ability of a stabilized form of Env (envelope glycoprotein)—SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named “SOS” and an isoleucine-to-proline point mutation-named “IP” at residue 559)—to elicit an immune response in young rhesus macaques. The SOSIP protein was engineered to activate naïve B cells expressing germline antibody precursors. Male and female infant macaques were immunized with wild-type SOSIP (SOSIP) or germline-targeting SOSIP (GT1.1), followed by a SOSIP booster. Both SOSIP and GT1.1 induced a protective immune response, but only GT1.1 induced VRC01-like bnAb precursors—antibodies that bind Env’s CD4-binding site and provide the broadest possible protection. These results represent a possible childhood HIV immunization strategy that would elicit protective immunity before sexual debut.
- Intrinsic Link Between PGRN and GBA1 D409V Mutation Dosage in Potentiating Gaucher Disease
Gaucher disease (GD) is an autosomal recessive disorder and one of the most common lysosomal storage diseases. GD is caused by mutations in the GBA1 gene that encodes glucocerebrosidase (GCase), a lysosomal protein involved in glyocolipid metabolism. Progranulin (PGRN, encoded by GRN) is a modifier of GCase, and GRN mutant mice exhibit a GD-like phenotype. The researchers in this study aimed to understand the relationship between GCase and PGRN. They generated a panel of male and female mice with various doses of the GBA1 D409V mutation in the GRN-/- background and characterized the animals’ disease progression using biochemical, pathological, transcriptomic, and neurobehavioral analyses. Homozygous (GRN-/-, GBA1 D409V/D409V) and hemizygous (GRN-/-, GBA1 D409V/null) animals exhibited profound inflammation and neurodegeneration compared to PG96 wild-type mice. Compared to homozygous mice, hemizygous mice showed more profound phenotypes (e.g., earlier onset, increased tissue fibrosis, shorter life span). These findings offer insights into GD pathogenesis and indicate that GD severity is affected by GBA1 D409V dosage and the presence of PGRN.
Read more in the archive.
