Prof. Karim Labib FRSE Karim studied Natural Sciences at the University of Cambridge. He first learned about DNA replication through the lectures of Ron Laskey, in whose lab Karim spent the summer of 1988. In 1990, Karim moved to the University of Oxford as a PhD student with Paul Nurse (Nobel Prize for medicine, 2001) and used the fission yeast Schizosaccharomyces pombe to study how eukaryotic cells make sure that their chromosomes are copied just once per cell cycle. Subsequently, Karim received a research fellowship from the European Molecular Biology Organisation (EMBO) to spend a year in Salamanca with Sergio Moreno (1993-1994). Karim then returned to Oxford for two years with Stephen Kearsey (1995-1997), where he first learnt about the Mcm2-7 proteins that were thought to be important regulators of the initiation step of DNA replication in eukaryotic cells, but were of unknown molecular function. After seven years training as a yeast geneticist and cell biologist, Karim moved to the Clare Hall Research Laboratories in London (now incorporated into the Francis Crick institute) and joined the group of John Diffley, who was renowned for developing innovative biochemical approaches to explore the workings of the DNA replication machinery. Karim developed new tools with which to inactivate Mcm2-7 very rapidly in budding yeast cells, and used these tools to show that Mcm2-7 were not only essential for the initiation of DNA replication, but were also required for the progression of DNA replication forks. Together with evidence from Stephen P. Bell's lab that Mcm2-7 appeared to move with DNA replication forks, and work by Yukio Ishimi showing that a sub-complex of three of the Mcm2-7 proteins was able to unwind short stretches of DNA in vitro, Karim's discovery indicated that Mcm2-7 represented the essential DNA helicase at eukaryotic replication forks. In 2001, Karim started his own research group at the Cancer Research UK Manchester Institute (previously the Paterson Institute for Cancer Research), supported by a Senior Cancer Research Fellowship. By systematically inactivating all of the essential yeast proteins of previously unknown function, Karim's group identified three new components of the eukaryotic DNA replication machinery, which Hiro Araki's group in Japan showed were part of a new complex of four proteins called GINS. Karim's group showed that GINS was essential for both initiation and elongation, just like Mcm2-7 and another factor called Cdc45. Subsequently, Karim's group found that GINS formed a very tight complex with Mcm2-7 and Cdc45 at replication forks. Michael Botchan's lab isolated the analogous complex from fruit fly embryos (they called it 'CMG' for Cdc45-MCM-GINS) and showed that it had DNA helicase activity. Karim's group showed that the CMG helicase forms the stable core of a larger multi-protein assembly at DNA replication forks, which we now know as the eukaryotic replisome. Karim's group found that some components of the yeast replisome control the progression of DNA replication forks, whilst other replisome components (including the CMG helicase itself) also act as histone chaperones and are important to preserve repressive chromatin during the process of chromosome duplication. In 2013, Karim moved to the University of Dundee as Professor of Genome Integrity, and his group joined the MRC Protein Phosphorylation and Ubiquitylation Unit in the School of Life Sciences. Karim's group found that disassembly of the replisome during DNA replication termination is driven by ubiquitylation of the CMG helicase, leading to a disassembly reaction that requires the Cdc48 'unfoldase'. Much of the work of Karim's group in Dundee is now focussed on studying the complex ubiquitylation pathways that control CMG ubiquitylation and disassembly in animal cells. In 2004, Karim was selected as a member of the EMBO Young Investigator Programme, which brings together many of the best young scientists from all over Europe. More recently, Karim spent six years as part of the selection committee for this programme, serving as chair between 2016 and 2019. In 2010, Karim was elected as a member of EMBO and was awarded the Hooke medal by the British Society for Cell Biology. In 2016 Karim was elected as a Fellow of the Royal Society of Edinburgh, Scotland's National Academy.
Prof. Karim Labib FRSE
Karim studied Natural Sciences at the University of Cambridge. He first learned about DNA replication through the lectures of Ron Laskey, in whose lab Karim spent the summer of 1988. In 1990, Karim moved to the University of Oxford as a PhD student with Paul Nurse (Nobel Prize for medicine, 2001) and used the fission yeast Schizosaccharomyces pombe to study how eukaryotic cells make sure that their chromosomes are copied just once per cell cycle. Subsequently, Karim received a research fellowship from the European Molecular Biology Organisation (EMBO) to spend a year in Salamanca with Sergio Moreno (1993-1994). Karim then returned to Oxford for two years with Stephen Kearsey (1995-1997), where he first learnt about the Mcm2-7 proteins that were thought to be important regulators of the initiation step of DNA replication in eukaryotic cells, but were of unknown molecular function. After seven years training as a yeast geneticist and cell biologist, Karim moved to the Clare Hall Research Laboratories in London (now incorporated into the Francis Crick institute) and joined the group of John Diffley, who was renowned for developing innovative biochemical approaches to explore the workings of the DNA replication machinery. Karim developed new tools with which to inactivate Mcm2-7 very rapidly in budding yeast cells, and used these tools to show that Mcm2-7 were not only essential for the initiation of DNA replication, but were also required for the progression of DNA replication forks. Together with evidence from Stephen P. Bell's lab that Mcm2-7 appeared to move with DNA replication forks, and work by Yukio Ishimi showing that a sub-complex of three of the Mcm2-7 proteins was able to unwind short stretches of DNA in vitro, Karim's discovery indicated that Mcm2-7 represented the essential DNA helicase at eukaryotic replication forks. In 2001, Karim started his own research group at the Cancer Research UK Manchester Institute (previously the Paterson Institute for Cancer Research), supported by a Senior Cancer Research Fellowship. By systematically inactivating all of the essential yeast proteins of previously unknown function, Karim's group identified three new components of the eukaryotic DNA replication machinery, which Hiro Araki's group in Japan showed were part of a new complex of four proteins called GINS. Karim's group showed that GINS was essential for both initiation and elongation, just like Mcm2-7 and another factor called Cdc45. Subsequently, Karim's group found that GINS formed a very tight complex with Mcm2-7 and Cdc45 at replication forks. Michael Botchan's lab isolated the analogous complex from fruit fly embryos (they called it 'CMG' for Cdc45-MCM-GINS) and showed that it had DNA helicase activity. Karim's group showed that the CMG helicase forms the stable core of a larger multi-protein assembly at DNA replication forks, which we now know as the eukaryotic replisome. Karim's group found that some components of the yeast replisome control the progression of DNA replication forks, whilst other replisome components (including the CMG helicase itself) also act as histone chaperones and are important to preserve repressive chromatin during the process of chromosome duplication. In 2013, Karim moved to the University of Dundee as Professor of Genome Integrity, and his group joined the MRC Protein Phosphorylation and Ubiquitylation Unit in the School of Life Sciences. Karim's group found that disassembly of the replisome during DNA replication termination is driven by ubiquitylation of the CMG helicase, leading to a disassembly reaction that requires the Cdc48 'unfoldase'. Much of the work of Karim's group in Dundee is now focussed on studying the complex ubiquitylation pathways that control CMG ubiquitylation and disassembly in animal cells. In 2004, Karim was selected as a member of the EMBO Young Investigator Programme, which brings together many of the best young scientists from all over Europe. More recently, Karim spent six years as part of the selection committee for this programme, serving as chair between 2016 and 2019. In 2010, Karim was elected as a member of EMBO and was awarded the Hooke medal by the British Society for Cell Biology. In 2016 Karim was elected as a Fellow of the Royal Society of Edinburgh, Scotland's National Academy.