Programs and Activities Highlights
- R24 Modern Equipment Fact Sheet
ORIP updated its fact sheet for the R24 Modern Equipment Program with up-to-date information in March 2024. ORIP updated previous program numbers and ensured that current notice of funding opportunity due dates are accurate. This fact sheet is one of several fact sheets that are valuable resources for potential investigators to learn about ORIP, ORIP-supported resources, and programs.
- Morehouse School of Medicine Site Visit
ORIP program staff conducted a virtual final site visit to the Morehouse School of Medicine (MSM) on March 4, 2024, to conclude the 20-year oversight period of grants C06RR016561 and C06RR017571. These construction awards funded the renovation of animal care facility and research laboratory spaces that supported MSM’s broad research portfolio, including cancer, cardiovascular disease, neuroscience, HIV and other infectious diseases, and community and population health. These infrastructure updates have expanded the capacity of office and research spaces and increased funding from federal and non-federal programs.
- Construction Site Visits
Between January and March 2024, ORIP’s Division of Construction and Instruments (DCI) performed 8 site visits to the recipient institutions of 11 construction (C06) grants. A closeout site visit to the recently completed Interdisciplinary Substance Use & Brain Injury Center at the University of New Mexico allowed DCI to learn about this construction project and assess the facility operation. The final site visits to 10 grant facilities, of which 5 were funded by the American Recovery and Reinvestment Act (ARRA) grants, allowed DCI to evaluate the impact, usage, and maintenance of these facilities during their 20-year (10-year for ARRA grants) beneficial occupancy. These facilities include animal housing facilities, medical imaging facilities, and centers focused on immunology, infectious disease, and eye research.
- Medical College of Wisconsin Site Visit
ORIP program staff conducted a virtual final site visit to the Eye Institute building at the Medical College of Wisconsin (MCW) on February 21, 2024, to conclude the 20-year oversight period of grant C06RR016511. This project included the conversion of clinical and administrative space on the seventh floor to research laboratories and associated core support laboratories, as well as the renovation of 20-year-old research laboratories on the eighth floor. As a major component of MCW’s neuroscience initiative, this expansion in vision research efforts allowed the recruitment of more faculty and students and thus increased research and training capabilities. Major outcomes include more than 320 papers and chapters, 12 awarded patents, 17 pending patents, 3 licensed products, and 3 spin-out companies.
- Reissue ORIP Concept Clearance: Shared Instrumentation Program
ORIP presented this concept clearance for reissue at the January 2024 NIH Council of Councils meeting. The initiative supports purchases of state-of-the-art, commercially available instruments to NIH-funded investigators. The program is based on shared use, which makes it cost efficient and beneficial to thousands of investigators in hundreds of institutions nationwide.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- Targeting Pancreatic Cancer Metabolic Dependencies Through Glutamine Antagonism
Pancreatic ductal adenocarcinoma (PDAC) cells rely on glutamine (Gln) for proliferation and redox balance. Traditional Gln metabolism inhibitors faced resistance. Yet, treating PDAC cells with 6-diazo-5-oxo-L-norleucine (DON) induced metabolic crisis in vitro. In mice models (of unspecified sex), the pro-drug version, sirpiglenastat (DRP-104), reduced tumor growth without DON’s toxicity, enhancing survival in combination with trametinib, an extracellular signal-regulated kinase (ERK) pathway inhibitor. These findings suggest broad Gln metabolism targeting as a therapeutic strategy for PDAC, with potential enhancement through ERK pathway inhibition, offering promising avenues for treatment.
- Sensory Neurons Promote Immune Homeostasis in the Lung
JAK1-dependent type 2 cytokines contribute to chronic inflammatory diseases. Inserting a human JAK1 gain-of-function variant into both male and female mice led to spontaneous atopic dermatitis–like skin disease but unexpected resistance to lung inflammation when expression was stroma-specific. JAK1 in vagal sensory neurons suppressed airway inflammation by regulating Calcb/CGRPβ expression, which in turn suppressed group 2 innate lymphoid cell function and allergic airway inflammation. These findings suggest tissue-specific roles of JAK1 in sensory neurons, offering insights for precision medicine through optimized JAK inhibitors.
- Integrative Single-Cell Characterization of a Frugivorous and an Insectivorous Bat Kidney and Pancreas
This study examines cellular and molecular differences in the kidneys and pancreases of insectivorous and frugivorous bats using single-cell sequencing. Frugivorous bats show changes in kidney cell populations related to fluid and electrolyte balance, and in pancreas cell populations associated with insulin regulation. These bats exhibit molecular characteristics similar to human diabetes. Understanding these differences may offer therapeutic insights. This research sheds light on the evolution of frugivory in mammals and its implications for human health.
- Serine-129 Phosphorylation of Α-Synuclein Is an Activity-Dependent Trigger for Physiologic Protein–Protein Interactions and Synaptic Function
Phosphorylation of α-synuclein at serine-129 (α-syn Ser129P) is a hallmark of synucleinopathies. Unlike wild-type α-syn, α-syn Ser129P exhibits restricted brain expression, indicating intrinsic regulation. Surprisingly, inhibiting Ser129P impairs activity-dependent synaptic attenuation by α-syn, revealing its normal function. Neuronal activity enhances Ser129P, promoting protein–protein interactions crucial for α-syn function at synapses. AlphaFold2-driven modeling and simulations suggest Ser129P induces conformational changes facilitating interactions with binding partners. This study provides insights into the role of Ser129 in synucleinopathies and potential implications for drug development.
- Viral Afterlife: SARS-CoV-2 as a Reservoir of Immunomimetic Peptides That Reassemble Into Proinflammatory Supramolecular Complexes
The mechanism behind severe inflammatory responses in severe COVID-19 remains unclear. Researchers investigate the inflammatory potential of fragmented viral components from high SARS-CoV-2 loads. Machine learning analysis identifies viral peptides mimicking host antimicrobial peptides (xenoAMPs), particularly LL-37. These xenoAMPs, enriched in SARS-CoV-2, assemble viral RNA into complexes capable of multivalent binding to Toll-like receptor-3, amplifying cytokine secretion in various cell types. Administration of these complexes to mice mimics inflammatory responses seen in COVID-19 patients. Understanding this mechanism sheds light on COVID-19 pathogenesis and may inform therapeutic strategies.
Read more in the archive.
