Selected Grantee Publications
- Clear All
- 2 results found
- Aquatic Vertebrate Models
- nhlbi
- 2021
MIC-Drop: A Platform for Large-scale In Vivo CRISPR Screens
Parvez et al., Science. 2021.
https://pubmed.ncbi.nlm.nih.gov/34413171/
CRISPR screens in animals are challenging because generating, validating, and keeping track of large numbers of mutant animals is prohibitive. These authors introduce Multiplexed Intermixed CRISPR Droplets (MIC-Drop), a platform combining droplet microfluidics, single-needle en masse CRISPR ribonucleoprotein injections, and DNA barcoding to enable large-scale functional genetic screens in zebrafish. In one application, they showed that MIC-Drop could identify small-molecule targets. Furthermore, in a MIC-Drop screen of 188 poorly characterized genes, they discovered several genes important for cardiac development and function. With the potential to scale to thousands of genes, MIC-Drop enables genome-scale reverse genetic screens in model organisms. Supported by ORIP (R24OD017870), NIGMS, and NHLBI.
Cell-Specific Transcriptional Control of Mitochondrial Metabolism by TIF1γ Drives Erythropoiesis
Rossmann et al., Science. 2021.
https://pubmed.ncbi.nlm.nih.gov/33986176/
Transcription and metabolism both influence cell function but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. The authors discovered that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon's bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage. Supported by ORIP (R24OD017870), NIGMS, NHLBI, and NCI.