Research Fellow in Synthetic Biology - Liverpool, United Kingdom - Liverpool John Moores University

Liverpool John Moores University

Verified Company

Liverpool, United Kingdom

3 weeks ago

Posted by:

Tom O´Connor

beBee Recruiter

Description

Large serine integrases (LSIs; derived from lysogenic phages) mediate precise site-specific DNA recombination (integration, excision, or inversion), leaving not a single nick in the DNA backbone.

Control of LSI directionality is uniquely simple. The integrase itself catalyses phage insertion, but not the reverse (excision) reaction.

Excision requires a second protein called a recombination directionality factor (RDF), that binds its cognate integrase and alters its conformation in an unknown manner that somehow inhibits integration and activates excision.

LSI-RDF pairs can catalyse the insertion of large payloads into genomic DNA without relying on host DNA repair (unlike CRISPR-Cas-based systems) and can scarlessly and controllably reverse those insertions (unlike any other system).

The project's aim is to develop large serine integrases as tools for constructing and manipulating genetic circuits for use in synthetic cells.

This project seeks to (1) through bioinformatics and protein engineering, eliminate the current bottleneck in identifying cognate RDFs for individual LSIs; (2) understand, through cryo-electron microscopy and biochemistry, how an RDF interacts with its cognate integrase to control the reaction direction; and (3) enhance the usefulness of RDFs by engineering new control mechanisms into them.

You will be responsible for the planning, design and execution of the research programme and will ideally have expertise in the broadly defined fields of Biochemistry, Synthetic Biology, and/or Molecular Biology.

Experience with the tools of bioinformatics, structural biology and/or nucleic acid biochemistry is preferred. This work will include analyses using standard molecular cloning techniques, microbiology, and enzymes for DNA manipulation.

It will also involve purification of serine integrases and other proteins; analysis of the properties of these proteins _in vivo_ and i_n vitro_; design and implementation of experiments to test and analyse the interaction of integrases and their RDFs.

Applicants should be eager to learn new skills and systems, and should have effective communication, teamworking and problem-solving skills. Successful applicants will be actively involved in regular communication with (and possibly visit) the Rice lab (University of Chicago). You will collaborate in the preparation of scientific reports and manuscripts, and participate in selected meetings and conferences.

Closing date: 31st January 2023.