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Project

Microfluidics for the synthetic biology of modular endolysins

Endolysins are enzymes that degrade the bacterial cell wall, resulting in a quick cell death. They are

recognized as a novel class of antibiotics with high potential. A unique feature that differentiates

them from all know antibiotic classes is their modular nature, comprising two to four modules with

a dedicated function. Swapping of these modules yields antibiotics with desired and improved

properties in a process that we call the synthetic biology of modular proteins. We have developed a

technique U+2013VersaTile Shuffling U+2013which excels in the convenience, efficiency and throughput of

module shuffling and we can now produce millions of modular variants per day. With this project

we aim to build microdroplet-based assays using recent advances in microfluidics to study the

structure-activity relationship between the modular composition and antibacterial properties of this

novel class of antibiotics, and to select the best modular endolysin variants out of millions of

variants. Such ultra-high-throughput selection technology for protein engineering will deliver

candidate endolysins for a personalized medicine of infectious diseases, or to prevent or treat

rapidly emerging bacterial epidemics in agriculture and food industry. In extension, the combination

of VersaTile Shuffling and microdroplet-based assays for protein engineering will spur similar

research projects with modular proteins in our research group in the field of protein engineering.

Date:1 Jan 2018 →  31 Dec 2018
Keywords:Microfluidics
Disciplines:Medical molecular engineering of nucleic acids and proteins