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.