The scientists presenting in the November webinar will be Dr James Checco, Assistant Professor at University of Nebraska-Lincoln, and Dr Martin Spinck, Postdoctoral Fellow at the MRC Laboratory of Molecular Biology.
Date: 07-11-2025
Time: 3:00-4:00 pm
Venue: an online Zoom seminar
Dr James Checco, Assistant Professor at University of Nebraska-Lincoln
Title: Affinity-driven aryl diazonium labeling to study peptide-receptor interactions
Endogenous peptides (neuropeptides and peptide hormones) act as cell-to-cell signaling molecules to carry out complex tasks in living systems. Characterizing the molecular mechanisms of endogenous peptides represents a significant goal to understand how living systems function in both healthy and disease states, and to identify novel therapeutic targets. To better understand the molecular mechanisms of intercellular communication, our group focuses on developing and utilizing chemical biology approaches to understand endogenous peptides and probe peptide-receptor interactions. This seminar will focus on our recent progress using peptides modified with aryl diazonium groups for the affinity-driven covalent modification of peptide receptors on living cells. Such covalent capture can be useful for probing peptide-receptor interactions, visualizing receptor localization and trafficking, as the starting point for novel modulators of signaling, and to identify receptors for bioactive peptides. Overall, our research combines approaches from chemical biology, bioanalytical chemistry, and synthetic chemistry to advance our understanding of specific cell-cell signaling pathways, identify new pathways for further exploration, and provide innovative starting points for future therapeutics.
Dr Martin Spinck, Postdoctoral Fellow at MRC LMB, Cambridge
Title: Automated orthogonal tRNA generation
The ability to generate orthogonal, active tRNAs 鈥� central to genetic code expansion and reprogramming 鈥� is still fundamentally limited. Here we develop Chi-T, a method for the de novo generation of orthogonal tRNAs. Chi-T segments millions of isoacceptor tRNA sequences into parts and then assembles chimeric tRNAs from these parts. Chi-T fixes the parts, containing identity elements, and combinatorially varies all other parts to generate chimeric sequences; Chi-T filters the variable parts and chimeric sequences to minimize host identity elements. We show that experimentally characterized orthogonal tRNAs are more likely to have predicted minimum free energy cloverleaf structures, and Chi-T filters for sequences with a predicted cloverleaf structure. We report RS-ID for the identification of synthetases that may acylate the tRNAs generated by Chi-T. We computationally identify new orthogonal tRNAs, and engineer an orthogonal pair generated by Chi-T/RS-ID to direct non-canonical amino acid incorporation, in response to both amber codons and sense codons, with an efficiency comparable to benchmark genetic code expansion systems.
Spinck, M., Guppy, A. & Chin, J.W. Automated orthogonal tRNA generation. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01782-3
Date: 07-11-2025
Time: 3:00-4:00 pm
Venue: an online Zoom seminar
Dr James Checco, Assistant Professor at University of Nebraska-Lincoln
Title: Affinity-driven aryl diazonium labeling to study peptide-receptor interactions
Endogenous peptides (neuropeptides and peptide hormones) act as cell-to-cell signaling molecules to carry out complex tasks in living systems. Characterizing the molecular mechanisms of endogenous peptides represents a significant goal to understand how living systems function in both healthy and disease states, and to identify novel therapeutic targets. To better understand the molecular mechanisms of intercellular communication, our group focuses on developing and utilizing chemical biology approaches to understand endogenous peptides and probe peptide-receptor interactions. This seminar will focus on our recent progress using peptides modified with aryl diazonium groups for the affinity-driven covalent modification of peptide receptors on living cells. Such covalent capture can be useful for probing peptide-receptor interactions, visualizing receptor localization and trafficking, as the starting point for novel modulators of signaling, and to identify receptors for bioactive peptides. Overall, our research combines approaches from chemical biology, bioanalytical chemistry, and synthetic chemistry to advance our understanding of specific cell-cell signaling pathways, identify new pathways for further exploration, and provide innovative starting points for future therapeutics.
Dr Martin Spinck, Postdoctoral Fellow at MRC LMB, Cambridge
Title: Automated orthogonal tRNA generation
The ability to generate orthogonal, active tRNAs 鈥� central to genetic code expansion and reprogramming 鈥� is still fundamentally limited. Here we develop Chi-T, a method for the de novo generation of orthogonal tRNAs. Chi-T segments millions of isoacceptor tRNA sequences into parts and then assembles chimeric tRNAs from these parts. Chi-T fixes the parts, containing identity elements, and combinatorially varies all other parts to generate chimeric sequences; Chi-T filters the variable parts and chimeric sequences to minimize host identity elements. We show that experimentally characterized orthogonal tRNAs are more likely to have predicted minimum free energy cloverleaf structures, and Chi-T filters for sequences with a predicted cloverleaf structure. We report RS-ID for the identification of synthetases that may acylate the tRNAs generated by Chi-T. We computationally identify new orthogonal tRNAs, and engineer an orthogonal pair generated by Chi-T/RS-ID to direct non-canonical amino acid incorporation, in response to both amber codons and sense codons, with an efficiency comparable to benchmark genetic code expansion systems.
Spinck, M., Guppy, A. & Chin, J.W. Automated orthogonal tRNA generation. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01782-3
