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Project

A microfluidic platform to screen engineered lasso peptides for therapeutic potential

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly expanding class of chemically and structurally-diverse bacterial natural products. Many exhibit therapeutically important biological activities, such as antibiotic, antifungal, insecticidal, immunomodulating and anti-cancer activities. The relaxed substrate specificity of RIPP biosynthetic enzymes, together with the increasing availability of methods to efficiently introduce multiple site-directed mutations, opens the door to generating large libraries of RiPP variants that can be screened for improved pharmaceutical properties. However, there is currently no suitable screening platform that can handle such enormous amounts of variants. We envision that a droplet-based microfluidic platform is the ideal technology to handle high numbers of engineered RiPP variants. A microfluidic droplet is the smallest bioreactor imaginable; it is the ultimate miniaturization of a microtiter plate well. This allows for ultrahigh-throughput parallelization of assays with an analysis rate of up to 2000 variants per second. In this project, we therefore aim to develop a first in its kind droplet-based microfluidic platform to screen libraries of engineered RiPPs for variants with new biological activities that can be used for therapeutic applications. Due to my experience with protein engineering and the development of microfluidic platforms, I am convinced that I am the best candidate for this project.

Date:1 Nov 2021 →  Today
Keywords:Biosynthetic engineering of ribosomally synthesized and post-translationally modified peptides (RiPPs), High-throughput screening with microfluidics
Disciplines:Microbiology not elsewhere classified, Metagenomics, Microfluidics/flow chemistry, Medical molecular engineering of nucleic acids and proteins, Industrial molecular engineering of nucleic acids and proteins