Progress on Theme 3: Specialized Research Training in Animal Models and Related Resources
Programs and Activities Highlights
- T32 and T35 Directors Consortium
ORIP staff facilitated a discussion on program and grant topics among the T32 and T35 directors on June 17, 2024. Topics included key changes for training grant applications, peer review, criteria for fellowship applications, and carryover requests. - Opportunities for Veterinary Scientists at NIH
ORIP staff participated in a virtual discussion with veterinary students on opportunities for veterinary scientists at NIH, which was hosted through the University of Pennsylvania School of Veterinary Medicine on June 24, 2024. - Notice of Funding Opportunity Reissue (PA-24-176) and ORIP Information Update for PA-24-176
The purpose of the NIH Mentored Research Scientist Development Award (K01) is to provide support and protected time (3–5 years) for an intensive, supervised career development experience in the biomedical, behavioral, or clinical sciences leading to research independence. When NIH reissued the notice of funding opportunity, ORIP added specific information to the funding opportunity PA-24-176 in April 2024. For investigator-initiated applications submitted in response to the parent funding opportunity announcement—Mentored Research Scientist Development Award (Parent K01 – Independent Clinical Trial Not Allowed)—ORIP support is limited to graduate veterinarians (i.e., D.V.M.s, V.M.D.s, and equivalents) only. The K01 allows 4 years of protected time to develop an awardee’s research career. Once a K01 has been obtained, the awardee is permitted, and actively encouraged, to apply for additional research grants anytime during the tenure of their K award. - T32 and T35 Directors Consortium
Two ORIP program staff members attended the T32/T35 Directors Consortium Meeting on March 11, 2024. ORIP participated in a panel discussion on the topic of leveraging the T35 experiences to create a pipeline for qualified T32 trainees. ORIP’s T32 Postdoctoral Program for Veterinarians trains highly qualified veterinarians for research careers in biomedical areas related to comparative medicine. - Special Emphasis Research Career Award in Comparative or Translational Medicine
These guidelines summarize policies governing the Special Emphasis Research Career Award (SERCA) in Comparative or Translational Medicine, which is offered by ORIP’s Division of Comparative Medicine. Potential applicants should also refer to these guidelines for the Mentored Research Scientist Development Award (Parent K01), PA-20-190. Differences between SERCA and the Parent K01 are described in these guidelines. This award is intended solely to provide support and protected time to graduate veterinarians for an intensive, supervised career development experience in the biomedical sciences leading to research independence.
ORIP-Supported Research Highlights
- Controlled Stiffness of Direct-Write, Near-Field Electrospun Gelatin Fibers Generates Differences in Tenocyte Morphology and Gene Expression
Tendinopathy is associated with mobility issues, and the cell–matrix interactions involved in the development of tendinopathy are not fully understood. In this study, researchers fabricated micron-scale fibrous scaffolds that mimic native collagen fiber size and orientation. They reported that matrix metalloproteinase and proteoglycans (possible indicators of tendinopathy) were more upregulated in the presence of high-stiffness fibers than low-stiffness fibers. The authors’ findings suggest that scaffolds can serve as in vitro models for tendinopathy. Additionally, their work suggests that matrix mechanical properties contribute to cell–matrix interactions during tendinopathy formation. - Transcriptome- and Proteome-Wide Effects of a Circular RNA Encompassing Four Early Exons of the Spinal Muscular Atrophy Genes
Spinal muscular atrophy (SMA) is a leading genetic cause of mortality in infants and often results from a deficiency of deletions of or mutations in the SMN1 gene. In this study, researchers report the transcriptome- and proteome-wide effects of overexpression of C2A 2B-3–4, a circular RNA produced by SMN1 and SMN2, in cells. They report that C2A-2B-3–4 is associated with expression of genes associated with chromatin remodeling, transcription, spliceosome function, ribosome biogenesis, lipid metabolism, cytoskeletal formation, cell proliferation, and neuromuscular junction formation. More work is needed to investigate the role of these genes in processes associated with SMA and other pathological conditions, including cancer and male infertility. - Potent HPIV3-Neutralizing IGHV5-51 Antibodies Identified From Multiple Individuals Show L Chain and CDRH3 Promiscuity
Human parainfluenza virus 3 fusion glycoprotein (HPIV3 F), responsible for facilitating viral entry into host cells, is a major target of neutralizing antibodies that inhibit infection. More work is needed to understand these dynamics. Researchers characterized the genetic signatures, epitope specificity, neutralization potential, and publicness of HPIV3-specific antibodies identified across multiple individuals (sex not specified). From this work, they identified 12 potently neutralizing antibodies targeting three nonoverlapping epitopes on HPIV3 F. Six of the antibodies used immunoglobulin heavy variable gene (IGHV5-51). These antibodies used different L chain variable genes (VL) and diverse H chain CDR 3 (CDRH3) sequences. These findings help elucidate the genetic and functional characteristics of HPIV3-neutralizing antibodies and indicate the existence of a reproducible H chain variable–dependent antibody response associated with VL and CDRH3 promiscuity. - Ultrasoft Platelet-Like Particles Stop Bleeding in Rodent and Porcine Models of Trauma
Platelet transfusions are the current standard of care to control bleeding in patients following acute trauma, but their use is limited by short shelf life and limited supply. Immunogenicity and contamination risks also are a concern. Using ultrasoft and highly deformable nanogels coupled to fibrin-specific antibody fragments, researchers developed synthetic platelet-like particles (PLPs) as an alternative for immediate treatment of uncontrolled bleeding. They report that PLPs reduced bleeding and facilitated healing of injured tissue in mice, rat, and swine models (sex not specified) for traumatic injury. These findings can inform further translational studies of synthetic PLPs for the treatment of uncontrolled bleeding in a trauma setting. -
Pathogenesis and Virulence of Coronavirus Disease: Comparative Pathology of Animal Models for COVID-19
Researchers have used animal models that can replicate clinical and pathologic features of severe human coronavirus infections to develop novel vaccines and therapeutics in humans. The purpose of this review is to describe important animal models for COVID-19, with an emphasis on comparative pathology. The highlighted species included mice, ferrets, hamsters, and nonhuman primates. Knowledge gained from studying these animal models can help inform appropriate model selection for disease modeling, as well as for vaccine and therapeutic developments.