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Science Papers on Transcriptomics-Fueled Drug Target Discovery Approach, Food Crop Domestication

Using a novel transcriptomics-guided drug target discovery strategy, a group of scientists from the University of Groningen have identified receptor ligands that could be therapeutic targets for conditions involving lung damage such as chronic obstructive pulmonary disease (COPD). Finding drugs with regenerative potential remains a key challenge in pharmacology, particularly for respiratory conditions. In a study appearing in Science Advances this week, the researchers describe a transcriptomics-guided drug target discovery strategy that they apply to COPD, focusing on gene signatures differentially expressed in the disease and in mice exposed to cigarette smoke. They find several drug targets with regenerative potential including EP and IP prostanoid receptor ligands, which had the most profound therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Using single-cell RNA sequencing, the scientists uncovered circadian clock and cell cycle/apoptosis signaling pathways that were differentially expressed in alveolar epithelial progenitor cells in patients with COPD and in a COPD model, which prevented "similar beneficial effects may be operative in diseases affected by similar defects in alveolar progenitors such as acute respiratory distress syndrome and pulmonary fibrosis," the study authors write. "Overall, these data provide promising therapeutic strategies to specifically address defective lung repair in respiratory diseases."

A comparison of the domestication pathways in the economically important food crops maize and rice has revealed a gene involved in kernel row number in corn that could be altered to increase yield. The study, which appears in this week's Science, also shows that manipulating a related gene in rice could boost that plant's yield as well. Maize and rice were independently domesticated about 100,000 years ago yet share a number of agriculturally desirable traits. The traits appear to have undergone convergent selection in distinct cereal lineages, but it is unknown if they were driven by conserved genes, which could potentially be targeted in breeding programs. To investigate, a group led by scientists from China Agricultural University analyzed the genomes of maize and its evolutionary ancestor teosinte, discovering the quantitative trait locus associated with kernel number. By fine mapping this genomic region, the researchers found the gene KRN2 — which has a homolog in rice called OsKRN2 — linked to WD40 proteins that regulate grain number. Knocking out the two genes boosted grain yield by 10 percent and 8 percent in maize and rice, respectively, with no apparent trade-offs in other agronomic traits. "These findings suggest that the identification of genes that have undergone convergent selection could further inform breeding efforts of cereals," the study's authors conclude. " A deep understanding of the conservation of selection-driven genetic elements will not only enable more rapid innovation of the maize and rice germplasm but also inform knowledge-driven de novo domestication of new crops to meet the diverse needs of food production worldwide."

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