PhD (Dartmouth), FRSC
Research Area: Cell Biology
I study chromosome movements during cell division. We try to understand the entire process of cell division, but concentrate on chromosome movements during anaphase.
During anaphase, chromosomes move slowly to a spindle pole, near the speed of a tectonic plate. One simple question is: what produces the force that causes the chromosome to move poleward? All agree that the spindle fibre associated with the chromosome contains microtubules, and that the fibre propels the chromosomes poleward, but there is no agreement on how this is done. Most work concentrates on microtubules, but there are other components in spindle fibres including actin and myosin; no-one knows what the different components do. One way we studied this was to irradiate small portions of spindles using a focussed beam of ultraviolet light (a UV microbeam) or a laser microbeam; after irradiation we studied chromosome or spindle pole movement in the irradiated cells using video microscopy and we looked at the structure of the irradiated spot using immunofluorescence (confocal) and electron microscopy. Chromosomes moved normally after the UV severed both microtubules and actin (Forer et al., 2003; Sheykhani et al., 2013a), so we argue that chromosomes move because a spindle matrix propels the chromosome’s spindle fibre poleward (review in Johansen et al., 2011; Forer et al., 2015). We implicated actin and myosin in force production using inhibitors (e.g., Sheykhani et al., 2013b), and we identified titin, another muscle protein, in spindles (Fabian et al., 2007); thus the matrix might contain actin, myosin and titin.
We also study “signalling” between chromosomes. Irradiation of a spindle fibre in anaphase temporarily blocks the motion of the associated chromosome, but it also blocks the motion of the partner chromosome (moving to the opposite pole). The partner stops moving because of a “signal” sent across the interzone: when the interzone is irradiated first, only the chromosome associated with the fibre stops moving, not the partner (Yin and Forer, 1996). There are other ‘signals’ as well: in “distance segregation”, unpaired chromosomes nonetheless move to opposite poles, but we have no idea how they signal to each other (Ferraro-Gideon et al., 2013, 2014; Forer et al., 2013).
Forer et al. (2015) Protoplasma 252: 775-781.
Ferraro-Gideon et al. (2014) Protoplasma 251: 127-143.
Ferraro-Gideon et al. (2013) Cell Biology Internatioinal 37: 892-898.
Forer A. et al. (2013) Protoplasma 250: 1045-1055.
Sheykhani et al. (2013a). Cytoskeleton 70: 241-259.
Sheykhani et al. (2013b). European J Cell Biol. 92: 175-186.
Fabian, L. Xia, X., ... and Forer, A. (2007). Journal of Cell Science 120: 2190-2204.
Forer, A. et al. (2003). Cell Motility and the Cytoskeleton 56: 173-192.
Ilagan, A. and Forer, A. (1997). Cell Motility and the Cytoskeleton 36: 266-275.
Yin, B. and Forer, A. (1996). J. Cell Science 109: 155-163.