Image of Karim Labib
Professor Karim Labib
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Background Information

Karim Labib was born and educated in Lancashire, before studying Natural Sciences at the University of Cambridge, where he became fascinated with chromosome replication and its relevance to human cancer, through the lectures of Ron Laskey, in whose lab he spent the summer of 1988. After graduation in 1989, Karim spent seven years studying the regulation of chromosome replication in fission yeast, firstly as a PhD student with Sir Paul Nurse at Oxford University, then as an EMBO postdoctoral fellow with Sergio Moreno in Salamanca, and finally back in Oxford with Stephen Kearsey. In 1997, Karim joined the group of John Diffley at the Clare Hall research laboratories in London, and developed a method for the rapid inactivation of budding yeast proteins, based on the ‘heat-inducible degron’. Using this trick, Karim made the key observation that the Mcm2-7 proteins are required for the progression of DNA replication forks. The Mcm2-7 proteins were already known as initiation factors and were of particular interest, as their regulated association with chromatin limits DNA replication to one round per cell cycle. We now know that the Mcm2-7 complex forms the catalytic core of the essential DNA helicase at eukaryotic replication forks.

In 2001, Karim received a Senior Cancer Research Fellowship to start his own group at the Cancer Research UK Manchester Institute, with the aim of using degron technology to develop a new form of ‘functional genomics’, with which to inactivate all the essential yeast proteins of previously unknown function. This led to the discovery of novel cell cycle factors, including DNA replication proteins that are now known as the components of the ‘GINS complex’, which represented a key ‘missing link’ in the replication field, and were the last conserved DNA replication factors to be identified. Critically, Karim’s group discovered that GINS makes a stable complex at DNA replication forks with Mcm2-7 and Cdc45, to form what we now as the active form of the essential Cdc45-MCM-GINS DNA helicase. Moreover, Karim’s group showed that the Cdc45-MCM-GINS helicase associates with many other factors at replication forks as part of the eukaryotic replisome, which has thus become the major focus of the group. Karim is keen to understand how the replisome contributes to the regulation of genome integrity and epigenetics in diverse eukaryotic species. A key part of this work will be to understand how the replisome is regulated by post-translational modifications. A better understanding of the replication machinery should help to identify novel targets for future anti-cancer drugs.

Having been a member of the EMBO Young Investigator Programme from 2004 to 2007, Karim was elected a member of EMBO in 2010 and was awarded the Hooke medal by the British Society for Cell Biology. In October 2013, Karim joined the MRC Protein Phosphorylation and Ubiquitylation Unit, as well as becoming ‘Professor of Genome Integrity’ in the College of Life Sciences in Dundee.