Programs and Activities Highlights
- 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.
- University of Missouri Site Visit
ORIP program staff conducted a virtual final site visit to the University of Missouri on May 10, 2024, to conclude the 20-year oversight period of two grants. Grant C06RR018822 provided funds to establish the National Swine Research and Resource Center, which serves as a core facility for NIH-funded investigators and provides services in model curation, health monitoring, research, model creation, workshops, and training. Major research highlights include heart and kidney transplants. Grant C06RR017353 provided funding to establish the Center for Diabetes and Cardiovascular Health. The original grant objectives were to house and promote collaborations among NIH-funded investigators. Over the course of 20 years, investigators in the facility have been awarded about $100 million in funding by NIH and other sources, provided mentoring and training for more than 70 individuals, hosted 24 visiting scholars, and published nearly 300 peer reviewed articles.
- Association of Biomolecular Resource Facilities Annual Meeting
An ORIP staff member presented on the S10 instrumentation programs at the Association of Biomolecular Resource Facilities meeting, held April 21–24, 2024, in Minneapolis, Minnesota. The presentation was attended by more than 100 people. ORIP also was represented on a panel in a breakout session. The S10 programs are based on shared use, which increases cost efficiency and benefits for thousands of investigators in hundreds of institutions nationwide.
- Construction Site Visits
Between April and June 2024, ORIP’s Division of Construction and Instruments performed 13 final site visits to facilities funded by 21 construction grants. These facilities include animal housing facilities, medical imaging facilities, and centers focused on ophthalmology, immunology, infectious diseases, neuroscience, pharmaceutical, diabetes, cardiovascular, and behavioral research. Through these visits, the program staff were able to evaluate the impact, usage, and maintenance of these facilities during their 20-year (10-year for six American Recovery and Reinvestment Act grants) beneficial occupancy periods.
- 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.
Read more in the archive.
Research Highlights from Investigators Using ORIP-Supported Instrumentation
- Rare Genetic Variation in Fibronectin 1 (FN1) Protects Against APOEε4 in Alzheimer's Disease
This study explores protective genetic variants in APOEε4 carriers against Alzheimer’s disease (AD). Through whole-genome sequencing of elderly APOEε4 carriers (sex not specified) without dementia, the authors identified rare coding variants enriched in extracellular matrix (ECM)–related genes, including FN1 and COL6A2, which are expressed at the blood–brain barrier (BBB). The rs140926439 variant in FN1 was associated with reduced AD risk and delayed disease onset. Postmortem and in vivo studies confirmed increased FN1 and COL6A2 at the BBB in APOEε4 carriers with AD. Zebrafish models (both sexes) showed that FN1 loss of function reduced gliosis and enhanced microglial responses, suggesting the gene’s role in APOEε4-mediated AD pathology. Targeting such ECM proteins as FN1 could offer therapeutic avenues for AD.
- Designer Peptide-DNA Cytoskeletons Regulate the Function of Synthetic Cells
Engineering artificial cells requires a dynamic cytoskeleton. Inspired by actin-binding proteins, researchers created peptide-DNA crosslinkers with varying designs. These peptide filaments form tunable bundles via DNA hybridization. In cell-sized droplets, the crosslinkers guide cytoskeletal structures to specific locations, controlling payload diffusion. Complementary DNA handles allow reversible payload recruitment. Heat triggers shape changes in droplets by adjusting DNA melting temperatures. This modular peptide-DNA design is a powerful strategy for assembling synthetic cells.
- Tumour-Selective Activity of RAS-GTP Inhibition in Pancreatic Cancer
Broad-spectrum RAS inhibition that targets KRAS, HRAS, and NRAS mutations could benefit cancer patients with RAS-driven tumors. RMC-7977, a selective inhibitor for both mutant and wild-type GTP-bound RAS, was tested in various pancreatic ductal adenocarcinoma (PDAC) in vitro models, where more than 90% of cases involve KRAS mutations. The inhibitor showed significant anti-tumor activity with well-tolerated exposure levels. Tumors experienced apoptosis and sustained proliferative arrest, whereas normal tissues showed only temporary proliferation decreases without apoptosis. In a female mouse model, RMC-7977 extended survival, but Myc copy number gain led to resistance. Combining RMC 7977 with TEAD inhibition in vitro overcame this resistance, supporting the potential of RAS-GTP inhibition in PDAC therapy.
- Prolonged Exposure to Lung-Derived Cytokines Is Associated With Activation of Microglia in Patients With COVID-19
Survivors of pneumonia, including SARS-CoV-2 pneumonia, face increased risks of cognitive dysfunction and dementia. Inflammation is key, with lung-derived pro-inflammatory cytokines affecting microglia, the brain cells linked to cognitive issues. A study measured cytokines during respiratory failure in male and female patients, noting higher cumulative cytokine exposure in COVID-19 cases. Microglia from COVID-19 patients showed activation signatures linked to inflammation. Corticosteroids reduced specific cytokine expressions in COVID 19. These findings highlight the role of prolonged lung inflammation in cognitive dysfunction, emphasizing the need to explore the role of microglia in pneumonia-related cognitive issues further.
- A Distinct Fusobacterium nucleatum Clade Dominates the Colorectal Cancer Niche
Fusobacterium nucleatum (Fn), a microbiota that is typically found in the oral cavity in humans, has been shown to be enriched in human colorectal cancer (CRC) tissues. In this study, researchers performed a comparative genomics analysis of human CRC Fn strains. They found that CRC-associated strains belong predominantly to Fn subspecies animalis (Fna) clade C2, which shows enhanced metabolic potential and CRC colonization ability. Using female mice and human (sex not specified) CRC tissue and stool samples, the researchers confirmed Fna C2 enrichment in CRC. The authors suggest that Fna C2 could be a primary focus for future mechanistic studies and a potential pathway for therapeutic intervention in CRC.
Read more in the archive.
