Reflections on DNA – how do topoisomerases distinguish between left-handed and right-handed superhelices?
Supervisors:
Sean Colloms, School of Molecular Biosciences, University of Glasgow
Laura Spagnolo, School of Molecular Biosciences, University of Glasgow
Industry Partner - Inspiralis Ltd
Summary:
DNA is a long double-helical molecule. Every human cell contains 2 meters of DNA with ~600 million helical turns that must be entirely unwound during every cycle of replication. Topoisomerases are enzymes that cut and rejoin DNA to relieve the torsional stress (supercoiling) that builds up ahead of the replication fork due to this unwinding. Topisomerases also untangle any linkage remaining between daughter chromosomes at the end of replication. Topoisomerases are essential for replication and transcription in all DNA-based life, and are important anti-bacterial and anti-cancer drug targets.
In this NorthWestBio CASE studentship you will use site-specific recombination to generate novel catenated DNA substrates with different (left-handed and right-handed) chirality to study the mechanism used by topoisomerases to discriminate between over-winding, under-winding, and different types of tangling of the DNA double-helix. You will also use cryo-electron microscopy to study the structure of topoisomerases. This project will be carried out in association with Inspiralis, a small biotechnology company based in the Norwich Research Park specializing in topoisomerase-related products. You will learn a wide range of Molecular Biology, Biochemistry and Structural Biology techniques, including cryo-electron microscopy. You will benefit from a three-month training placement at Inspiralis where you will experience working in a commercial environment, carrying out research directed towards a commercial output and learning other aspects of Biotechnology from a business perspective.