Cell Division - Iain Hagan

After completing his PhD studies Iain went to Japan on a 4-year postdoctoral fellowship with Professor Mitsuhiro Yanagida in Kyoto University. He returned to the UK in 1993 with a Cancer Research Campaign Return Fellowship to establish a group in The University of Manchester. He continued to work in what later became the Faculty of Life Sciences at The University of Manchester, with further Cancer Research Campaign Fellowship support before moving to the Cancer Research UK Manchester Institute in 2001. In 1999 he was awarded the Human Frontier Science Program 10th Anniversary Medal and in 2001 was the recipient of the BSCB Hooke Medal. Iain is currently a Senior Group Leader at the CRUK MI. In 2009 he was elected to full membership of the European Molecular Biology Organisation (EMBO). In 2016, Iain was awarded a Wellcome Trust Investigator Award to study spatial and temporal control of mitotic commitment.


Cancer is a genetic disease of inappropriate cell proliferation.  Cell proliferation is a balance between increasing cell numbers, through cell division, and reducing them, through cell death.  Within the cell division cycle, the duplication of the genome in S phase is separated from its segregation in mitosis.  A complex structure called the mitotic spindle physically segregates the two genomes in mitosis.  Pathways that promote cell death are initiated when cells enter mitosis with incomplete or damaged DNA, or when they become trapped in mitosis as a consequence of errors in chromosome architecture or spindle function. Because cancers have inherently high levels of genome instability, it is possible to find levels of DNA or spindle damaging agents that can trigger death in tumour cells, while leaving normal tissue untouched.  Anti-mitotics and DNA damaging agents are therefore widely used in the clinic.

We exploit the simplicity and genetic malleability of yeast as a model system in which to identify fundamental principles in the control of the decisions to enter and exit mitosis.  We define the molecular detail of conserved cell cycle controls and key principles of cell division in yeast for subsequent, highly focused, studies in much more complex human cell line models.
There are two principle themes to our research: the role played by the centrosome in promoting mitotic commitment and exit and the properties and control of the protein phosphatases that drive cells out of division. As cell division is accompanied by a cessation of migration and morphogenesis, some of our studies address very specific aspects of cytoskeletal control of morphogenesis.


Selected Publications


Trotter EW, Hagan IM. (2020)
Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronized cell cycle progression in human cell culture.
Open Biology 10(10), 200200. PubMed abstract

Chan KY, Alonso-Nuñez M, Grallert A, Tanaka K, Connolly Y, Smith DL, Hagan IM. (2017)
Dialogue between centrosomal entrance and exit scaffold pathways regulates mitotic commitment.
Journal of Cell Biology 216(9):2795-2812. PubMed abstract

Grallert A, Boke E, Hagting A, Hodgson B, Connolly Y, Griffiths JR, Smith DL, Pines J, Hagan IM. (2015)
A PP1-PP2A phosphatase relay controls mitotic progression.
Nature 517(7532):94-8. PubMed abstract

Grallert A, Patel A, Tallada VA, Chan KY, Bagley S, Krapp A, Simanis V, Hagan IM. (2013)
Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast.
Nature Cell Biology 15(1):88-95. PubMed abstract

Tallada VA, Tanaka K, Yanagida M, Hagan IM. (2009)
The S. pombe mitotic regulator Cut12 promotes spindle pole body activation and integration into the nuclear envelope.
Journal of Cell Biology 185(5):875-88. PubMed abstract

Petersen J, Hagan IM.  (2005)
Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast. 
Nature 435(7041):507-12. PubMed abstract

Tanaka K, Petersen J, MacIver F, Mulvihill DP, Glover DM, Hagan IM. (2001)
The role of Plo1 kinase in mitotic commitment and septation in Schizosaccharomyces pombe.
EMBO Journal 20(6):1259-70. PubMed abstract

Bridge AJ, Morphew M, Bartlett R, Hagan IM. (1998)
The fission yeast SPB component Cut12 links bipolar spindle formation to mitotic control. 
Genes and Development  12(7):927-42. PubMed abstract

Hagan I, Yanagida M. (1992)
Kinesin related cut7 protein associates with mitotic and meiotic spindles in fission yeast. 
Nature 356(6364):74-6. PubMed abstract

Hagan I, Yanagida M. (1990)
Novel potential mitotic motor protein encoded by the fission yeast cut7+ gene.
Nature 347(6293):563-6. PubMed abstract

Postdoctoral Fellows
Asma Belbelazi
Daniela Eckert
Zoe Edwards
Lenka Halova
Pawan Singh
Sanjeeta Tamang

Scientific Officers
Eleanor Wendy Trotter
Keren Dawson

Graduate Students
Millie Jones
Zoe Lee