Programs and Activities Highlights
- Sex as a Biological Variable Policy for Studies Using Nonhuman Primates in Neuroscience Research
The NIH Office of Research on Women’s Health developed the NIH Policy on Sex as a Biological Variable (SABV), which builds on the importance of sex in biology, health, and disease, as well as the need for research to consider sex to be relevant for all people. In January 2024, NIH convened a virtual workshop to provide the neuroscience research community an opportunity to discuss challenges and potential solutions for applying the SABV policy fairly and consistently to nonhuman primate (NHP) studies. An ORIP staff member presented at the workshop as an invited panelist to provide ORIP's perspective on the NHP shortage, best utilization of existing resources, and issues regarding NHP use in neuroscience research.
- BioGRID: Resource Overview
ORIP published a video overview of the Biological General Repository for Interaction Datasets (BioGRID) program in January 2024. BioGRID is an open-access public database that uses structured curation to capture protein, genetic, and chemical interaction data from model organisms and humans.
- Limited Competition: Mutant Mouse Resource and Research Centers (U42 Clinical Trial Not Allowed) PAR-24-105
This notice of funding opportunity invites applications for the continued support and advancement of the Mutant Mouse Resource and Research Centers (MMRRCs). The MMRRC consortium is expected to facilitate research by identifying, acquiring, evaluating, characterizing, cryopreserving, and distributing mutant mouse strains to qualified biomedical investigators. A regional network of four MMRRCs and an Informatics, Coordination and Service Center collectively serve the needs of the biomedical research community for transgenic, knockout, and other genetically engineered mutant mice and related biomaterials. MMRRC strains are held to the highest standards to optimize reproducibility of studies and ensure scientific rigor and transparency; all submitted strains are thoroughly reviewed and documented and include additional quality control measures. The Program Director/Principal Investigator of each MMRRC is required to develop a small high-risk, high-return, research pilot project that complements the goals and needs of the MMRRC consortium.
- Oncology Models Forum Annual Meeting
An ORIP staff member presented ORIP’s rodent resources at the Oncology Models Forum Annual Meeting in December 2023. Topics of discussion at the meeting included discussed obstacles to answering translational questions in models, as well as potential approaches to overcome those obstacles.
- Knockout Mouse Phenotyping Program/International Mouse Phenotyping Consortium: Annual Fall 2023 Meeting
An ORIP program staff member attended the Knockout Mouse Phenotyping Program (KOMP2)/International Mouse Phenotyping Consortium (IMPC) Annual Fall Meeting, which was held in Houston, Texas, in November 2023. KOMP2 collaborates with IMPC to knockout and characterize all protein-coding genes in the mouse genome. ORIP’s participation in this meeting was required for monitoring the overall project progress and facilitating the exchange of scientific knowledge with international collaborators.
Read more in the archive.
ORIP-Supported Research Highlights
- Conjugation of HIV-1 Envelope to Hepatitis B Surface Antigen Alters Vaccine Responses in Rhesus Macaques
Researchers are interested in developing an HIV-1 vaccine that improves upon the regimen used in the RV144 clinical trial. The authors tested the hypothesis that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T-cell help and improve antibody production against HIV-1. Using juvenile rhesus macaques of both sexes, they evaluated the immunogenicity of their conjugate regimen. Their findings suggest that conjugate vaccination can engage both HIV-1 Env–specific and hepatitis B surface antigen–specific T-cell help and modify antibody responses at early time points. This work may help inform future efforts to improve the durability and efficacy of next-generation HIV vaccines.
- The Monarch Initiative in 2024: An Analytic Platform Integrating Phenotypes, Genes and Diseases Across Species
The Monarch Initiative aims to bridge the gap between the genetic variations, environmental determinants, and phenotypic outcomes critical for translational research. The Monarch app provides researchers access to curated data sets with information on genes, phenotypes, and diseases across species and advanced analysis tools for such diverse applications as variant prioritization, deep phenotyping, and patient profile matching. Researchers describe upgrades to the app, including scalable cloud-based infrastructure, simplified data ingestion and knowledge graph integration systems, enhanced data mapping and integration standards, and a new user interface with novel search and graph navigation features. A customized plugin for OpenAI’s ChatGPT allows the use of large language models to interrogate knowledge in the Monarch graph and increase the reliability of the responses of Monarch’s analytic tools. These upgrades will enhance clinical diagnosis and the understanding of disease mechanisms.
- Conduction-Dominated Cryomesh for Organism Vitrification
Vitrification-based cryopreservation via cryomesh is a promising approach for maintaining biodiversity, health care, and sustainable food production via long-term preservation of biological systems. The researchers conducted a series of experiments aimed at optimizing the cooling and rewarming rates of cryomesh to increase the viability of various cryopreserved biosystems. They found that vitrification was significantly improved by increasing thermal conductivity, reducing mesh wire diameter and pore size, and minimizing the nitrogen vapor barrier of the conduction-dominated cryomesh. Cooling rates increased twofold to tenfold in a variety of biosystems. The conduction-dominated cryomesh improved the cryopreservation outcomes of coral larvae, Drosophila embryos, and zebrafish embryos by vitrification. These findings suggest that the conduction-dominated cryomesh can improve vitrification in such biosystems for biorepositories, agriculture and aquaculture, and research.
- Investigation of Monoclonal Antibody CSX-1004 for Fentanyl Overdose
The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl and has led to more than 70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. The authors present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice of both sexes, CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Using a highly translational nonhuman primate model, squirrel monkeys of both sexes, for respiratory depression, they demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3–4 weeks. These data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.
- A Combined Adjuvant Approach Primes Robust Germinal Center Responses and Humoral Immunity in Non-Human Primates
Protein antigens require adjuvants for high immunogenicity, and delivery kinetics are a critical component of rational HIV vaccine design. Investigators employed a combined adjuvant approach (i.e., short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide, plus saponin/MPLA nanoparticles) with slow antigen delivery and potent immune-stimulating complexes in rhesus macaques of both sexes. They reported that pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells. These findings indicate that a combined adjuvant approach can augment humoral immunity by modulating immunodominance, and this work can be applied for the development of clinical therapeutics.
Read more in the archive.
