The next scientists presenting will be Dr Markus Weingarth (Utrecht University) and Dr Kilian Colas (University of Tokyo)
Date: 01-05-2026
Time: 1:00-2:00 pm
Venue: an online Zoom seminar (please register)
Dr Markus Weingarth
Associate Professor at Utrecht University
鈥淐racking Nature鈥檚 Recipes to Design Lipid-Targeting Antibiotics鈥�
Antimicrobial resistance is a global health threat, calling for new antibiotics. Good candidates could be peptide-based compounds that target special lipids that only exist in bacterial, but not in human cell membranes. These drugs kill pathogens without detectable resistance, which has generated considerable interest.
Here, using an integrative structural biology approach, we show that drugs that target special lipids in bacterial membranes use sophisticated supramolecular killing mechanisms1-4.
Dr Kilian Colas
Assistant Professor
Department of Chemistry, University of Tokyo
鈥淏est of both worlds: Lasso-Grafting peptide pharmacophores onto protein scaffolds鈥�
Grafting peptide pharmacophores onto scaffold proteins produces hybrid constructs that not only retain the high binding affinity of the source peptide, but also inherit the desirable properties of the scaffold, including high solubility and stability. Depending on the choice of scaffold, pharmacophores can be derived from previously identified peptides (Lasso-graft) or discovered de novo (Zero-start) via mRNA display. Choosing Ubiquitin as a model scaffold, we have developed a collection of grafted constructs called U-bodies with excellent binding affinities against a variety of challenging targets. U-bodies can be genetically encoded into plasmids, enabling both production in bacterial systems and intracellular expression in mammalian cells.
Date: 01-05-2026
Time: 1:00-2:00 pm
Venue: an online Zoom seminar (please register)
Dr Markus Weingarth
Associate Professor at Utrecht University
鈥淐racking Nature鈥檚 Recipes to Design Lipid-Targeting Antibiotics鈥�
Antimicrobial resistance is a global health threat, calling for new antibiotics. Good candidates could be peptide-based compounds that target special lipids that only exist in bacterial, but not in human cell membranes. These drugs kill pathogens without detectable resistance, which has generated considerable interest.
Here, using an integrative structural biology approach, we show that drugs that target special lipids in bacterial membranes use sophisticated supramolecular killing mechanisms1-4.
- Shukla, R. et al. Teixobactin kills bacteria by a two-pronged attack on the cell envelope. Nature 608, 390-396, doi:10.1038/s41586-022-05019-y (2022).
- Shukla, R. et al. An antibiotic from an uncultured bacterium binds to an immutable target. Cell 186, 4059-4073.e4027, doi:10.1016/j.cell.2023.07.038 (2023).
- Jekhmane, S. et al. Host defence peptide plectasin targets bacterial cell wall precursor lipid II by a calcium-sensitive supramolecular mechanism. Nature Microbiology 9, 1778-1791, doi:10.1038/s41564-024-01696-9 (2024).
- Ntallis, C., Martin, N., Edwards, A., Weingarth, M. (2025) Nature Reviews Microbiology, Bacterial cell envelope-targeting antibiotics
Dr Kilian Colas
Assistant Professor
Department of Chemistry, University of Tokyo
鈥淏est of both worlds: Lasso-Grafting peptide pharmacophores onto protein scaffolds鈥�
Grafting peptide pharmacophores onto scaffold proteins produces hybrid constructs that not only retain the high binding affinity of the source peptide, but also inherit the desirable properties of the scaffold, including high solubility and stability. Depending on the choice of scaffold, pharmacophores can be derived from previously identified peptides (Lasso-graft) or discovered de novo (Zero-start) via mRNA display. Choosing Ubiquitin as a model scaffold, we have developed a collection of grafted constructs called U-bodies with excellent binding affinities against a variety of challenging targets. U-bodies can be genetically encoded into plasmids, enabling both production in bacterial systems and intracellular expression in mammalian cells.
