PhD in Biochemistry

Department/Location: Department of Biochemistry, Central Cambridge/nPhD Position - Marie Curie network ON-Tract: Protein engineering of enzymes: in vitro directed evolution and machine learning-based elaboration of biocatalysis for synthesis./nA doctoral position is available for 3-years to work with Professor Florian Hollfelder at the Biochemistry Department of Cambridge University (https://hollfelder.bioc.cam.ac.uk/). The project is part of the Horizon Europe Eu Marie Curie Network ON-TRACT (www.on-tract.eu/) and involves collaborations with various EU and UK groups engaged in using oligonucleotides for therapeutic purposes, including anti-cancer therapy./nThis project will develop ultrahigh throughput for in vitro evolution of enzymes used in synthetic chemistry relevant for oligonucleotide constructs (chiral synthesis: IREDs, ligases). Starting from diverse libraries made by error-prone PCR, site-saturation mutagenesis and transposon-based InDel mutagenesis in vitro selections will be carried out, followed by long-read nanopore sequencing and deep mutational scanning of the screening output./nThis approach selects new, efficient enzymes, but also generates unique sequencefunction datasets that will be interpreted by regression and tree-based machine learning algorithms to obtain even better mutants and develop mechanistic hypotheses./nVarious collaborations with ON-TRACT network partners across Europe allow a particularly wide skills training, including organic synthesis, cell biological and medical work.