Programs and Activities Highlights
- Modern Equipment for Shared-use Biomedical Research Facilities
ORIP published PAR-24-259 to invite applications that enhance research operation using the revived S15 Small Instrumentation Grants mechanism. Complementing ORIP’s S10 programs in supporting its NIH-wide mission, the unique equipment program offers agility to meet emerging research needs and flexibility to adapt to various NIH priorities.
- Construction Awards to Institutions of Emerging Excellence
ORIP awarded three C06 construction grants to Institutions of Emerging Excellence in September 2024 under PAR-23-306 to build biomedical research and training facilities that focus on cardiovascular diseases, cancer, and other health disparities prevalent among Hispanic and African American populations. These grants are critically important to strategically support research activities that benefit community health by enabling institutions to address the health needs of the local and regional communities. The recipients were San Juan Bautista School of Medicine in Puerto Rico, Florida Agricultural and Mechanical University, and Tougaloo College in Jackson, Mississippi. The latter two are Historically Black Colleges and Universities.
- Cryopreservation Workshop Session III: Cryoresearch—Supporting Technology and Resources
The third session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held on September 30, 2024. Session III focused on enhancing the rigor, reproducibility, and applicability of animal research by covering advancements in physical infrastructure, technology, and resources that support cryobiology research. The session also discussed best practices for managing cryopreserved animal models and genetic resources.
- Funding Opportunity for Biomedical Research Facilities
ORIP issued PAR-25-061, Biomedical Research Facilities (C06 Clinical Trial Not Allowed) to invite applications for funding to modernize existing or construct new biomedical research facilities, a reissue of PAR-23-306. Applications from both research-intensive institutions and Institutions of Emerging Excellence in biomedical research from all geographic regions in the nation are strongly encouraged, and each project is expected to produce substantial long-term improvements to the institutional research infrastructure.
- S10 Post-Award Webinar and Panel Discussion
On September 26, 2024, ORIP conducted a webinar for S10 principal investigators (PIs) and institutional signing officials to clarify post-award requirements, share best practices from program officers (POs) and experienced S10 PIs, and provide answers to questions. This inaugural webinar was aimed at enhancing the quality and compliance of S10 reports, ultimately reducing the administrative burden on both PIs and POs. This webinar was well attended, with more than 200 participants.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- Giant Polyketide Synthase Enzymes in the Biosynthesis of Giant Marine Polyether Toxins
Researchers identified the “PKZILLAs,” massive polyketide synthase genes in the harmful algae Prymnesium parvum that are responsible for producing prymnesins—large polyether toxins linked to fish kills. PKZILLA-1 and PKZILLA-2 encode enormous proteins, each with more than 90 enzyme domains, producing precursors to A-type and B-type prymnesins. This discovery unveils the long-mysterious biosynthesis of these toxins, providing insights into the genetic and enzymatic mechanisms behind polyether production. It challenges previous size expectations in biological systems, offering new perspectives on polyketide biosynthesis.
- Noninvasive Targeted Modulation of Pain Circuits With Focused Ultrasonic Waves
This study explores noninvasive modulation of the anterior cingulate cortex using low-intensity transcranial-focused ultrasound to treat chronic pain. In a randomized crossover trial with 20 male and female patients, 60% experienced significant pain reduction immediately after active stimulation, with sustained effects on days 1 and 7, compared with minimal improvements with sham stimulation. Pain was reduced by 60% immediately post-stimulation and by 43% and 33% on days 1 and 7, respectively. The approach was well tolerated, with only mild, temporary side effects, highlighting its potential as a noninvasive alternative to brain surgery for pain management.
- A Therapy for Suppressing Canonical and Noncanonical SARS-CoV-2 Viral Entry and an Intrinsic Intrapulmonary Inflammatory Response
This study used human lung organoids to explore lung responses to multiple SARS-CoV-2 strains, uncovering broader viral tropism than was known previously. SARS-CoV-2 can infect many lung cell types, entering via both ACE2 receptors and alternative pathways like macropinocytosis. Blocking endocytosis showed potential as an adjunctive therapy. The virus triggers an innate immune response, independent of immune cells, leading to rapid viral spread and mitochondrial apoptosis. Surfactant Protein-B was found to modulate immune signaling and reduce apoptosis, with exogenous surfactant showing therapeutic potential, shedding light on persistent inflammation in long COVID.
- Amyloid β Accelerates Age-Related Proteome-Wide Protein Insolubility
This study reveals a connection between aging, protein insolubility, and Alzheimer’s disease (AD). Using Caenorhabditis elegans, researchers discovered that amyloid beta (Aβ) expression promotes widespread protein insolubility, resembling the natural aging process. This “core insoluble proteome” (CIP) accelerates Aβ toxicity, potentially creating a vicious cycle in AD. The study also links CIP-associated biological processes to various chronic age-related diseases, suggesting a broader role for proteostasis loss in aging-related conditions. Notably, the gut-derived metabolite Urolithin A alleviates Aβ toxicity, highlighting its therapeutic potential for AD and other age-related diseases.
- A Humanized Mouse That Mounts Mature Class-Switched, Hypermutated and Neutralizing Antibody Responses
Researchers developed a humanized mouse model (THX, of both sexes) by grafting immunodeficient mice with human CD34+ cells and using 17β-estradiol to promote immune cell differentiation. THX mice reconstitute a functional human immune system, including diverse B- and T-cell populations, and can generate mature antibody responses. They successfully mount neutralizing responses to vaccines, such as the Pfizer-BioNTech COVID-19 vaccine, and can model autoimmune diseases like lupus. This model offers a robust platform for studying human immunity and developing vaccines and therapeutics.
Read more in the archive.
