Selected Grantee Publications
The Effect of Common Paralytic Agents Used for Fluorescence Imaging on Redox Tone and ATP Levels in Caenorhabditis elegans
Morton et al., PLOS One. 2024.
https://pubmed.ncbi.nlm.nih.gov/38669260
Caenorhabditis elegans is a highly valuable model organism in biological research. However, these worms must be paralyzed for most imaging applications, and the effect that common chemical anesthetics may have on the parameters measured—especially biochemical measurements such as cellular energetics and redox tone—is poorly understood. In this study, the authors used two reporters—QUEEN-2m for relative ATP levels and reduction-oxidation–sensitive green fluorescent protein for redox tone—to assess the impact of commonly used chemical paralytics. The results show that all chemical anesthetics at doses required for full paralysis alter redox tone and/or ATP levels, and anesthetic use alters the detected outcome of rotenone exposure on relative ATP levels and redox tone. Therefore, it is important to tailor the use of anesthetics to different endpoints and experimental questions and to develop less disruptive paralytic methods for optimal imaging of dynamic in vivo reporters. Supported by ORIP (P40OD010440, R44OD024963) and NIEHS.
Time of Sample Collection Is Critical for the Replicability of Microbiome Analyses
Allaband et al., Nature Metabolism. 2024.
https://pubmed.ncbi.nlm.nih.gov/38951660/
Lack of replicability remains a challenge in microbiome studies. As the microbiome field moves from descriptive and associative research to mechanistic and interventional studies, being able to account for all confounding variables in the experimental design will be critical. Researchers conducted a retrospective analysis of 16S amplicon sequencing studies in male mice. They report that sample collection time affects the conclusions drawn from microbiome studies. The lack of consistency in the time of sample collection could help explain poor cross-study replicability in microbiome research. The effect of diurnal rhythms on the outcomes and study designs of other fields is unknown but is likely significant. Supported by ORIP (T32OD017863), NCATS, NCI, NHLBI, NIAAA, NIAID, NIBIB, NIDDK, and NIGMS.
GenomeMUSter Mouse Genetic Variation Service Enables Multitrait, Multipopulation Data Integration and Analysis
Ball et al., Genome Research. 2024.
https://genome.cshlp.org/content/34/1/145.long
Advances in genetics, including transcriptome-wide and phenome-wide association analysis methods, create compelling new opportunities for using fully reproducible and widely studied inbred mouse strains to characterize the polygenetic basis for individual differences in disease-related traits. Investigators developed an imputation approach and implemented data service to provide a broad and more comprehensive mouse variant resource. They evaluated the strain-specific imputation accuracy on a “held-out” test set that was not used in the imputation process. The authors present its application to multipopulation and multispecies analyses of complex trait variation in type 2 diabetes and substance use disorders and compare these results to human genetics studies. Supported by ORIP (U42OD010921, P40OD011102, R24OD035408), NCI, NIAAA, NIDA, and NIDCD.