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Science Papers Take on Synthetic E. Coli, Epigenetic Analysis of Pediatric Gliomas

While it is hypothesized that removing sense codons and the transfer RNAs (tRNAs) that read them from the genome could enable the creation of cells with novel properties such as viral resistance and the ability to encode the biosynthesis of noncanonical heteropolymers, technical limitations have heretofore prevented testing this hypothesis. In this week's Science, however, a University of Cambridge team reports using synonymous codon compression and laboratory evolution to engineer a synthetic strain of Escherichia coli lacking tRNAs and the release factor that decodes TCG, TCA, and TAG codons. The resulting strain is unable to read canonical genetic code and is therefore completely resistance to a cocktail of viruses, they write. Additionally, they reassign the codons to enable the synthesis of proteins containing three distinct noncanonical amino acids, demonstrating the ability to create designer proteins.

Pediatric high-grade gliomas (pHGGs) are a common and deadly malignant brain tumor in children. Recent studies have linked the mutant histone protein H3K27M to more aggressive pHGG and a poorer overall response to therapy. Data have also shown that H3K27M drives gliomagenesis by altering epigenetic control of gene expression by altering epigenetic control of gene expression. The mechanism by which H3K27M acts in this way, however, is not fully understood. To address this, a group of Northwestern University scientists generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. As they report in Science Advances this week, they integrated RNA sequencing, chromatin immunoprecipitation sequencing, high-throughput chromosome conformation capture, and chromatin accessibility datasets from H3K27M and wild-type specimens to identify tumor-specific enhancers and regulatory networks for known oncogenes in pHGGs. They also uncover genomic structural variations that lead to enhancer hijacking events, resulting in aberrant oncogenic gene expressions. "This is, to our best knowledge, the first comprehensive genomic characterization of its kind for pHGG, lending new insight into mechanisms of transcription regulation in these tumors and revealing previously unknown therapeutic vulnerabilities," the study's authors write.

The Scan

Tens of Millions Saved

The Associated Press writes that vaccines against COVID-19 saved an estimated 20 million lives in their first year.

Supersized Bacterium

NPR reports that researchers have found and characterized a bacterium that is visible to the naked eye.

Also Subvariants

Moderna says its bivalent SARS-CoV-2 vaccine leads to a strong immune response against Omicron subvariants, the Wall Street Journal reports.

Science Papers Present Gene-Edited Mouse Models of Liver Cancer, Hürthle Cell Carcinoma Analysis

In Science this week: a collection of mouse models of primary liver cancer, and more.