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 studied this was to irradiate small portions of spindles using a focussed beam of ultraviolet light (a UV microbeam) or avisible-light 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 confocal immunofluorescence microscopy 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. 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).
In our most recent work 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). We don’t really know yet what tethers do, but initial experiments indicate that tethers signal between separating chromosomes to regulate their velocities of motion (Sheykhani e al., 2017). We are trying to understand what tethers are made of and what they do.
Fabian et al. (2007). Journal of Cell Science 120: 2190-2204.
Fegaras and Forer (2018). Protoplasma 255: 1205–1224
Forer et al. (2003). Cell Motility and the Cytoskeleton 56: 173-192.
Forer et al. (2017) European Journal of Cell Biology 96 :504–514
Sheykhani et al. (2013a). Cytoskeleton 70: 241-259.
Sheykhani et al. (2013b). European J Cell Biol. 92: 175-186.
Sheykhani et al. (2017) Cytoskeleton 74:91–103