Group Leader:
Iain Hagan
After completing my PhD studies I went to Japan on a 4-year postdoctoral fellowship with Professor Mitsuhiro Yanagida in Kyoto University. I returned to the UK in 1993 with a Cancer Research Campaign Return Fellowship to establish a group in The University of Manchester. I 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 Paterson Institute for Cancer Research in 2001. In 1999 I was awarded the Human Frontier Science Program 10th Anniversary Medal and in 2001 was the recipient of the BSCB Hooke Medal. I am currently a Senior Group Leader at the Paterson Institute for Cancer Research.
Postdoctoral Fellows
Marisa Alonso Nuñez
Marisa Madrid
Associate Scientist
Agnes Grallert
Graduate Students
Dorota Feret
Avinash Patel
Elvan Boke
Yisu Wang
Cell Division Group - Sad
Work by Yanagida's group showed that, after a brief delay, cell cycle progression continues unchecked in mutants which have defects in chromosome segregation and the septum cleaves the cell in two (Uemura and Yanagida, 1984). If the nucleus remains in the centre of the cell this kills the cell with a cut phenotype (Hirano et al., 1986). If on the other hand the nucleus wanders from the centre before the septation event the division will produce an aploid and a diploid daughter cell.
We therefore use a screen devised by Nurse's group to screen for mutants that diploidise after a generation at the restrictive temperature (Bridge et al., 1998; Broek et al., 1991). We then incorporate a simple 5 minute staining procedure to visualise the chromatin and a fusion between a spindle pole body (SPB) component and GFP (Bridge et al., 1998) to identify those strains which had the characteristics of spindle (A, B) from a background of mitotic defects in other processes such as the function of the anaphase promoting complex (APC) (C) or of the kinetochore (D) (Grallert and Hagan, 2002). Immunofluorescence is then used in a secondary screen to visualise the microtubules, SPBs and chromatin and confirm that the mutants did have defects in spindle function.
We have identified a number of new spindle formation mutants e.g. (Grallert and Hagan, 2002). We anticipate that these mutations will tell us much about the molecules that are required for the proper function of the microtubules and microtubule organising centres. However, we have been surprised to find that mutants identified in this screen seem to play a critical role in regulating commitment to mitosis (Bridge et al., 1998; Grallert and Hagan, 2002).
references
Bridge, A. J., Morphew, M., Bartlett, R., and Hagan, I. M. (1998). The fission yeast SPB component Cut12 links bipolar spindle formation to mitotic control. Genes and Development 12, 927-942.
Broek, D., Bartlett, R., Crawford, K., and Nurse, P. (1991). Involvement of p34cdc2 in establishing the dependency of S-phase on mitosis. Nature 349, 388-393.
Grallert, A., and Hagan, I. M. (2002). Schizosaccharomyces pombe NIMA-related kinase Fin1, regulates spindle formation and an affinity of Polo for the SPB. EMBO Journal 21, 3096-3107.
Hirano, T., Funahashi, S., Uemura, T., and Yanagida, M. (1986). Isolation and characterization of Schizosaccharomyces pombe cut mutants that block nuclear division but not cytokinesis. EMBOJournal 5, 2973-2979.
Uemura, T., and Yanagida, M. (1984). Isolation of type-I and type-II DNA topoisomerase mutants from fission yeast - single and double mutants show different phenotypes in cell-growth and chromatin organization. EMBO Journal 3, 1737-1744.