Publications

C-GEM researchers developed a novel method called 3-Prime Adenosine-Retaining Aminoacyl–tRNA Isolation (PARTI), which determines precisely how much of a cellular tRNA is acylated, what it is acylated with, and whether it has been acylated once or twice. PARTI is an essential verification tool for optimizing… Read More »Breakthrough Article: Monitoring monomer-specific acyl–tRNA levels in cells with PARTI (Nucleic Acids Res, 2025)

C-GEM researchers developed a novel post-translational backbone editing reaction to replace a peptide bond with a C-C bond as diketones and heterocycles. This general strategy provides the first example of a C–C bond forming reaction to take place within the peptide backbone, as well as… Read More »Peptide Backbone Editing via Post-Translational O to C Acyl Shift (JACS, 2025)

C-GEM researchers found that a single atom change on tRNA—O to S on the 3′ terminal adenosine—does not hinder regular translation. Changing the 3’ oxo-ester on tRNA to a more reactive thioester had the potential to impact translation positively or negatively at multiple steps in… Read More »Thioesters Support Efficient Protein Biosynthesis by the Ribosome (ACS Cent Sci, 2025)

C-GEM researchers investigated whether preventing the binding of ribosomal protein bS1 could improve ribosome orthogonality. A current, common strategy for generating orthogonal ribosomes involves controlling mRNA and ribosome interactions by modifying the Shine-Dalgarno and anti-Shine-Dalgarno sequences, the sequence that sits upstream of the start codon… Read More »Role of Ribosomal Protein bS1 in Orthogonal mRNA Start Codon Selection (Biochemistry, 2025)

C-GEM researchers developed a fast, simple, and generalizable method to assay aminoacyl-tRNA synthetase activity by detecting the acylated tRNA product using liquid chromatography–mass spectrometry. C-GEM first developed this method as a way to identify aminoacyl-tRNA synthetase enzymes that accept non-α-amino acid substrates even at extremely… Read More »Direct and quantitative analysis of tRNA acylation using intact tRNA liquid chromatography–mass spectrometry (Nat Protoc, 2025)

C-GEM published a new paper in Nature Communications in collaboration with the Innovative Genomics Institute. Our researchers developed an RNA language model to predict mutations that could lead to improved structural stability. This model was used to predict mutations that could lead to improved thermostability… Read More »RNA language models predict mutations that improve RNA function (Nat Commun, 2024)

The templated synthesis of proteins containing non-canonical and expanded backbone monomers (collectively called nnAAs) promises to vastly expand the chemical space available to biological therapeutics and materials, but existing technologies remain limiting. Addressing these limitations requires a deeper understanding of how the translational mechanism is… Read More »New paper: β-amino acids reduce ternary complex stability and alter the translation elongation mechanism

Aminoacyl-tRNA synthetases (aaRSs) catalyze the condensation of ɑ-amino acid monomers with tRNA. The resulting aminoacyl-tRNAs are used as substrates by the ribosome to generate natural sequence-defined bio-polymers. The ribosomal synthesis of non-natural sequence-defined bio-polymers demands aaRS enzymes for non-natural monomers. Current aaRS engineering platforms rely… Read More »New paper: A translation-independent directed evolution strategy to engineer aminoacyl-tRNA synthetases

Proteins with extended or alternative backbones represent the next frontier in protein and biomaterial evolution. One extended backbone of great interest includes β-esters found in natural products and bioplastics. In this paper, the authors report that β2-hydroxy acids possessing both (R) and (S) absolute configuration… Read More »New paper: Incorporation of multiple β2-hydroxy acids into a protein in vivo using an orthogonal aminoacyl-tRNA synthetase

The ribosome is a ribonucleoprotein complex found in all domains of life. Its role is to catalyze protein synthesis, the messenger RNA (mRNA)-templated formation of amide bonds between α-amino acid monomers. Amide bond formation occurs within a highly conserved region of the large ribosomal subunit… Read More »New paper: Minimization of the E. coli ribosome, aided and optimized by community science