Nina Hartrampf, Associate Professor in the Department of Chemistry at the University of Zurich, has been awarded an ERC Starting Grant for LASSOVERSE – Lasso Peptides as Versatile Scaffolds for Peptide Engineering. The European Research Council announced the 2026 results on September 3.
Lasso peptides are among the more improbable structures biology produces. A ribosomally synthesized precursor is cyclized into a small macrolactam ring, typically seven to nine residues, formed between the N-terminal amine and an aspartate or glutamate side chain. The C-terminal tail is then threaded through that ring and locked in place by bulky residues sitting above and below it, giving a mechanically interlocked topology rather than a folded one. The result is a peptide that resists heat and proteases to a degree that ordinary linear or even macrocyclic peptides do not, which is precisely the property a therapeutic peptide needs and rarely has. Several are antibacterial – microcin J25, the best studied of them, inhibits bacterial RNA polymerase – and that combination of stability and antibiotic activity is what makes the class interesting now, as resistance narrows the options available to clinicians.
The obstacle has always been access. The threaded topology is kinetically trapped and installed by the biosynthetic enzymes themselves; solid-phase synthesis alone does not produce it, and heterologous expression yields only what a given gene cluster already encodes. Hartrampf’s group has been working the seam between the two approaches, pairing automated fast-flow peptide synthesis with in vitro enzymatic maturation to make precursor analogs chemically and let the lasso cyclase do the threading, work reported in the Journal of the American Chemical Society in 2024.
LASSOVERSE scales that idea into a program. The project will develop new routes to produce and modify lasso peptides, combining chemistry and biology to improve their properties and widen the chemical space the class can occupy – with the goal of converting a largely unexplored group of natural products into practical building blocks for new antimicrobial agents.
The 2026 Starting Grant call was the most competitive on record: 4,807 proposals, 421 awards, an 8.8 percent success rate, and €705 million committed. Each grant runs up to €1.5 million over five years. Thirty-six went to researchers at Swiss host institutions, ten of them at the University of Zurich.
Hartrampf studied chemistry and biochemistry at Ludwig-Maximilians-Universität Munich and completed her doctorate with Dirk Trauner on natural product synthesis and chemical biology, then worked with Brad Pentelute at MIT on automated flow-based synthesis of peptides and proteins. Her laboratory in Zurich works on the chemical synthesis of post-translationally modified peptides and proteins – lasso peptides among them, alongside the oncogenic transcription factor MYC – and on flow methods for sequences that resist conventional synthesis. She received the American Peptide Society’s >a href="" target="_blank">Early Career Lectureship in 2025, the RSC Emerging Investigator Award in Protein and Peptide Science in 2024, the DECHEMA Award in 2024, and the Swiss Chemical Society’s Werner Prize in 2026.
The American Peptide Society congratulates Nina Hartrampf on her success.
