Programs and Activities Highlights
- NIH Focus Group Meeting on Strategy II of ORIP’s Strategic Plan
In July 2024, ORIP staff members organized and participated in an NIH Focus Group Meeting on Strategy II (Innovative Instruments and Equipment to Accelerate Research Discoveries) of ORIP’s strategic plan. The meeting focused on progress towards Strategy II activities, and ORIP gathered feedback for its next strategic plan. A total of 11 NIH subject matter experts from different institutes, centers, and offices attended the meeting.
- Fourteenth Comparative Medicine Resource Directors Meeting—Breakout Session
The Fourteenth Comparative Medicine Resource Directors (CMRD) meeting was held on August 6–7, 2024. This biennial meeting serves as a pivotal platform for ORIP-supported resource directors to share cutting-edge information, discuss advancements, foster collaborations, and explore future directions for resource management and development in comparative medicine. Centered on the theme of advancing biomedical research through integrative approaches and innovations, the meeting highlighted emerging complementary models, technologies, and methodologies. A breakout session dedicated to instruments allowed participants to discuss strategies for enhancing support for instrumentation and facilities, as well as potential future directions for resource optimization.
- S10 Instrumentation Fact Sheet
ORIP revised its fact sheet on the S10 Instrumentation Programs. ORIP updated previous program numbers and ensured that current funding opportunity due dates are accurate. This fact sheet is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- University of California, San Francisco, Site Visit
ORIP program staff conducted a virtual final site visit to the University of California, San Francisco (UCSF), on April 29, 2024, to conclude the 20-year oversight period of three grants. Grant C06RR014517 funded the renovation of the eighth floor of the Medical Sciences Building at the UCSF School of Pharmacy to house the new Pharmacogenetics Program. The space is occupied by 18 researchers, has resulted in several high-impact publications, and has attracted significant funding from private and public sources. Grant C06RR016267 supported the expansion and renovation of a biosafety level 3 facility at UCSF’s Institute of Neurodegenerative Diseases. The facility enabled faculty, postdoctoral researchers, and technicians at UCSF to further research on the human prions that cause Creutzfeldt-Jakob disease. Grant C06RR016490 was used to create the Program of Craniofacial and Skeletal Biology. The supported space houses the laboratories of five principal investigators, an administrative office, and core facilities for microarray analysis, which is a central resource for the Parnassus Mouse Microarray Consortium.
- National IDeA Symposium of Biomedical Research Excellence
The ninth National IDeA Symposium of Biomedical Research Excellence (NISBRE), a national scientific meeting to showcase the scientific and training accomplishments of the Institutional Development Award (IDeA) Program of NIGMS, took place June 16–19, 2024, in Washington, D.C. The goal of the conference was to maximize opportunities for networking and collaborations; it was attended by undergraduate and graduate students, postdoctoral fellows, junior and senior faculty, and staff. A “Meet the Funders” session provided opportunities for the attendees to interact with NIH’s programmatic staff from different institutes and centers—including NIGMS, NIDDK, NCI, NIAID, and the Office of the Director—for program- and funding-related queries. NIGMS collaborates with the ORIP Division of Construction and Instruments (DCI) and co-funds grants supported by DCI’s S10 Shared Instrumentation Programs. An ORIP staff member was a panelist on the “Meet the Funders” session and shared information on programs managed by DCI and ORIP, including the S10 Instrumentation Programs and equipment programs.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- Generation of Locus Coeruleus Norepinephrine Neurons From Human Pluripotent Stem Cells
Researchers developed a method to generate human locus coeruleus norepinephrine (LC-NE) neurons from pluripotent stem cells, achieving 40–60% yield. These neurons display key characteristics, such as neurotransmitter release, pacemaker activity, and response to stimuli. Single-nucleus RNA sequencing confirmed their identity and differentiation pathway. Engineered with an NE sensor, these neurons reliably detect extracellular NE levels. This breakthrough offers a valuable platform for studying psychiatric and neurodegenerative diseases and advancing drug discovery.
- Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice
This study investigates how early life exposure to the pollutant tetrachlorodibenzofuran (TCDF) disrupts gut microbiota and impairs metabolic health in male mice. Findings show reduced levels of beneficial bacteria (Akkermansia muciniphila), short-chain fatty acids, and gut hormones in exposed mice, leading to long-term metabolic dysregulation. These disruptions were transferable to germ-free mice, suggesting the microbiome plays a crucial role in mediating the effects of pollutants. The research highlights the persistent health impacts of short-term pollutant exposure on the microbiome, with potential implications for obesity and metabolic diseases.
- PI3Kγ Inhibition Circumvents Inflammation and Vascular Leak in SARS-Cov-2 and Other Infections
This study identifies the signaling protein PI3Kγ as a key regulator of immune cell recruitment and inflammation in severe infectious diseases, including SARS-CoV-2 and methicillin-resistant Staphylococcus aureus. PI3Kγ promotes immune cell trafficking and immune-suppressive transcription, contributing to tissue damage, fibrosis, and organ failure. Inhibiting PI3Kγ with the drug eganelisib improved survival in disease models by reducing inflammation, vascular leakage, and cytokine storms. These findings highlight PI3Kγ as a promising therapeutic target for mitigating inflammatory lung damage in severe infections.
- Structural Basis of Cfr-Mediated Antimicrobial Resistance and Mechanisms to Evade It
This study presents high-resolution structures of the Cfr-modified bacterial ribosome, providing insights into antibiotic resistance mechanisms. Cfr-mediated methylation of A2503 in 23S ribosomal RNA causes an allosteric rearrangement of nucleotide A2062, reducing the effectiveness of peptidyl transferase center inhibitors. The structures also reveal how the antibiotics iboxamycin and tylosin engage with the modified ribosome. These findings advance our understanding of Cfr-mediated resistance and offer a foundation for developing strategies to overcome antibiotic resistance in Gram-positive bacteria.
- APOE4 Homozygosity Represents a Distinct Genetic Form of Alzheimer's Disease
This study examined the impact of APOE4 homozygosity on Alzheimer's disease (AD) across clinical, pathological, and biomarker domains using data from the National Alzheimer's Coordinating Center and five large cohorts. Analyzing 3,297 male and female individuals pathologically and 10,039 clinically, the researchers found nearly all APOE4 homozygotes displayed AD pathology and higher biomarker levels by age 55, with almost full penetrance of abnormal amyloid levels by age 65. Symptom onset was significantly earlier, at 65.1 years, with biomarker changes resembling those in autosomal dominant AD. However, amyloid and tau positron emission tomography scans showed no differences in the dementia stage, suggesting distinct genetic underpinnings for APOE4 homozygotes in AD.
