Team:Paris Bettencourt
Protein scaffolds for star-shaped antimicrobial peptides
Antibiotic overuse in livestock industry is one of the major drivers to the antibiotic resistance evolution; motivating calls to reduce, replace, and re-think the antibiotic usage in animals. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Recently, a class of chemically-synthesized, star-shaped AMPs has been shown to exhibit broad-spectrum antimicrobial activity while maintaining biocompatibility with mammalian cells. In this project, we combinatorially fused a set of known AMPs to structurally diverse, self-assembling protein cores to produce star-shaped complexes. Over 200 fusions were designed and expressed in a cell-free system, then screened for activity, biocompatibility, and membrane selectivity. In addition, we selected 4 AMPs for rational mutagenesis (~12000 variants), and a subset of fusions for molecular dynamic modeling, to identify features of surface charge and star geometry that impact AMP performance. Overall, we aim to create a novel class of selective, non-toxic AMPs which are biologically-produced.
paris-bettencourt-2018@cri-paris.org 
