Programs and Activities Highlights
- 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.
- Fall 2023 Human Tissue and Organ Research Resource Steering Committee Meeting
ORIP program staff attended the Fall 2023 Meeting of the Human Tissue and Organ Research Resource (HTORR) Steering Committee held on November 29, 2023. HTORR, supported by grant U42OD011158, provides high-quality human biospecimens to investigators to facilitate scientific advances in biomedical research across multiple disciplines. HTORR programmatic updates were presented to the steering committee.
- 21st Annual Meeting of the Mutant Mouse Resource and Research Center Consortium
An ORIP program staff member attended the 21st Annual Meeting of the Mutant Mouse Resource and Research Center (MMRRC) Consortium in October 2023. The staff member presented an NIH update, participated in the discussions, advised on policies, evaluated the MMRRC program progress, and interacted with external advisory committee members.
- Complement Animal Research in Experimentation (Complement-ARIE) Program
An ORIP program staff member served as a co-facilitator at the public listening session for the Complement ARIE strategic planning meeting on October 2, 2023. Complement ARIE is focused on development, standardization, validation, and use of methods and approaches that will more accurately model human biology, known as new approach methodologies (NAMs). The listening session included key representatives from multiple sectors to gain insight into current opportunities and challenges regarding NAMs development.
Read more in the archive.
ORIP-Supported Research Highlights
- 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.
- Timing of Initiation of Anti-Retroviral Therapy Predicts Post-Treatment Control of SIV Replication
Researchers are interested in approaches to reducing viral rebound following interruption of antiretroviral therapy, but more work is needed to understand major factors that determine the viral “setpoint” level. Researchers previously assessed how timing of treatment can affect the frequency of rebound from latency. In the current study, the authors analyzed data from multiple studies of simian immunodeficiency virus (SIV) infection in rhesus macaques to further explore the dynamics and predictors of post-treatment viral control. They determined that the timing of treatment initiation was a major predictor of both the level and the duration of post-rebound SIV control. These findings could help inform future treatments.
- CD8+ T Cells Control SIV Infection Using Both Cytolytic Effects and Non-Cytolytic Suppression of Virus Production
HIV continuously evades and subdues the host immune responses through multiple strategies, and an understanding of these strategies can help inform research efforts. Using a mathematical model, investigators assessed whether CD8+ cells from male rhesus macaques exert a cytolytic response against infected cells prior to viral production. Their goal was to elucidate the possible mode of action of CD8+ cells on simian immunodeficiency virus (SIV)–infected cells. Models that included non cytolytic reduction of viral production best explained the viral profiles across all macaques, but some of the best models also included cytolytic mechanisms. These results suggest that viral control is best explained by the combination of cytolytic and non-cytolytic effects.
- Allelic Strengths of Encephalopathy-Associated UBA5 Variants Correlate Between In Vivo and In Vitro Assays
The UBA5 gene is associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder, in humans. The link between UBA5 variants and severity of DEE44, however, is not established. Investigators developed humanized fly models carrying a series of patient UBA5 variants. These flies showed differences in survival rates, developmental progress, life span, and neurological well-being. The severity of these defects correlated strongly with functional defects of UBA5 variants, allowing the classification of UBA5 loss-of-function variants into mild, intermediate, and severe allelic strengths in patients. This study provides resources for systematic investigation of the mechanistic link between UBA5 variants and DEE44 and for developing diagnostic approaches.
- Body Stiffness Is a Mechanical Property That Facilitates Contact-Mediated Mate Recognition in Caenorhabditis elegans
Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans. Chemical cues have been extensively studied as sensory cures of mate recognition, whereas the role of mechanical cues is largely unknown. Investigators studied the link of the hypodermis and body stiffness with mate recognition and mating efficiency in the worm C. elegans. They found that worm males assess attractiveness of potential mates though contact-mediated cues determined by species, sex, and developmental stages of the hypodermis. Body stiffness maintained by a group of cuticular collagens is critical for mate recognition and mating efficiency. This study suggests the important role of mechanosensory cues in mate recognition and provides a platform for mechanistically studying social behavior.
Read more in the archive.
