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 at a speed near that 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 that extends between chromosome and pole contains microtubules, and that the fibre propels the chromosomes poleward, but there is no agreement on how this is done. Most concentrate on microtubules, but other components in spindle fibres include actin and myosin; no-one knows what the different components do. One way we study this is to irradiate small portions of spindles using a focussed beam of ultraviolet light (a UV microbeam) or a visible-light laser microbeam; after irradiation we study the irradiated cells using video microscopy to detect what has changed and we look at the structure of the irradiated spot using confocal immunofluorescence microscopy and electron microscopy. Chromosomes move normally after the UV severs 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 Forer et al., 2015). We implicated actin and myosin in force production using inhibitors (e.g., Sheykhani et al., 2013b). Titin, another muscle protein, is also present (Fabian et al., 2007) so the matrix might contain actin, myosin and titin. A graduate student developed an in vivo system in which chromosomes move rapidly to poles after she depolymerised all spindle microtubules. This also shows that something other than microtubules causes chromosomes to move (Fegaras and Forer, 2018).
Most recently we discovered a new spindle component present in all animal cells, elastic tethers (like bungee cords) that extend between all separating chromosomes in anaphase (Forer et al., 2017). They are detected by cutting a piece off an anaphase chromosome: the arm fragment moves rapidly to the partner moving to the opposite pole as if pulled by a bungee cord. Other experiments indicate that tethers signal between separating chromosomes to regulate their velocities of motion (Sheykhani e al., 2017). Experiments by Emma Kite, another graduate student, indicate that tethers must be phosphorylated in order to be elastic. We suggest that tethers are composed of titin, the elastic protein responsible for elasticity in resting muscle.
Forer (2019) Biopolymers and Cell 35: 168
Fegaras and Forer (2018) Protoplasma 255: 1205–1224
Forer et al. (2017) European Journal of Cell Biology 96 :504–514
Sheykhani et al. (2017) Cytoskeleton 74:91–103
Forer et al. (2015) Protoplasma 252:775–781
Sheykhani et al. (2013a) Cytoskeleton 70: 241-259
Sheykhani et al. (2013b) European J Cell Biol. 92: 175-186.
Fabian et al. (2007) Journal of Cell Science 120: 2190-2204.
Forer et al. (2003) Cell Motility and the Cytoskeleton 56: 173-192.