Subject collection: Model Systems in Drug Discovery
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG
Editor's choice: Drug repurposing screens using worm and patient fibroblast models of PMM2-CDG led to the discovery of epalrestat, the first activator of PMM2 that targets the root cause of disease.
- Drug screens of NGLY1 deficiency in worm and fly models reveal catecholamine, NRF2 and anti-inflammatory-pathway activation as potential clinical approaches
Summary: Using worm and fly models of an ultra-rare congenital disorder of glycosylation, we performed repurposing screens and identified the FDA-approved drug aripiprazole as a clinical candidate.
- Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns
Summary: Large-scale, focused phenotyping campaigns provide data for thousands of mutant mouse genes, yielding key information for understanding rare human diseases and for developing novel drug therapies.
- A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects
Editor's choice: Mitochondria are conserved among eukaryotes and mutations in the factors that control their dynamics are causal for various human disorders. Hence, yeast models can be used for pharmacological screenings.
- Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
Summary: Using the vps13Δ strain, a yeast model of the neurodegenerative disorder chorea-acanthocytosis, we found that its defects can be overcome by reduction of calcineurin activity and/or type-I-myosin activation.
- Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation
Summary: A novel method for isolating and expanding primary neural crest cells, and establishment of reproducible temporal benchmarks of differentiation, provides a potential screening platform for developmental toxicity or therapeutic capacity.
- Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of Caenorhabditis elegans and its functional response to drugs
Editor's choice: Dystrophin-deficient Caenorhabditis elegans have measurably weak muscle strength and mitochondrial dysfunction, and they respond to drug treatments standard in treating human Duchenne muscular dystrophy.
- CRISPR-Cas9 human gene replacement and phenomic characterization in Caenorhabditis elegans to understand the functional conservation of human genes and decipher variants of uncertain significance
Summary: Here, we provide a CRISPR-Cas9 human gene replacement and phenomic characterization strategy to directly replace Caenorhabditis elegans genes with their human orthologs for disease variant modeling and therapeutic screening.
- The secret lives of cancer cell lines
Summary: A recent study in Nature demonstrated that ongoing mutational processes cause significant heterogeneity of widely used cancer cell lines. In this Editorial, the authors discuss the implications of these findings for the cancer and cell biology fields.
- Generation of mouse-zebrafish hematopoietic tissue chimeric embryos for hematopoiesis and host-pathogen interaction studies
Editor's choice: A new method to xenotransplant murine bone marrow cells into zebrafish blastulae that generates hundreds of transient chimeric animals with functional murine blood progenitor cells and innate immune cells.