Grant: Discovery Grants Program - Individual

I study the basic mechanisms that control chromosome movements during cell division. Chromosomes are duplicated in the nucleus; then one copy of each is distributed to each daughter cell during cell division. Errors can cause cell death, birth defects and cancers.    Chromosomes are distributed to daughter cells by the mitotic spindle, a temporary structure used solely to move chromosomes. First the duplicated chromosomes line up in the middle of the spindle. Spindle fibres connect them to opposite spindle poles, analogous to pairs of differently coloured boats lined up in the middle of a lake with the two boats (chromosomes) of each colour connected by a cable (spindle fibre) to a dock (spindle pole) on opposite sides of the lake. Each of the two docks gets one boat of each colour.     We study the forces that move chromosomes (boats) to their poles (docks). Most cell biologists think that boats are reeled in to their docks by winches at the dock, or winches at the boat, or both. Our experiments dispute this idea. We sever the cables (spindle fibres) with a laser microbeam and the boats still move to their dock. We suggest that the force for movement arises from water currents (from a spindle matrix). We reached the same conclusion from experiments in which the cables were dissolved (with a drug) and the boats then rapidly moved to one dock. Having boats move without cables allows us to identify and study the water (spindle matrix) components that may produce the force.    We also study communication between the chromosomes (boats). Each boat moves to its dock after a starter's whistle sounds (a global start signal). It often is assumed that this is all that is needed, but we have identified signals between boats that alters their motions to their docks. For example, boats of the same colour moving to opposite docks coordinate their speeds: when we weakly damage (but do not sever) the cable between a boat and its dock, both that boat and its partner boat (going to the other dock) stop moving. In this example the communication agents are "tethers", universal spindle components that we recently uncovered, analogous to bungee cords that connect boats of the same colour. When we cut a bungee cord (tether) with a laser, and then weakly damage the cable, communication between partner boats stops: the boats move independently. In other examples of communication there are no physical connections between the chromosomes. The overall goal of our research program is to understand the force production and inter-chromosome communication systems. Our short-term goal is to identify the non-cable (non-spindle fibre) force elements and to characterise the tethers and other elements of inter-chromosome coordination.    Importance: By knowing how chromosome movements occur and are controlled we can better understand the causes of errors in chromosome distributions that cause birth defects and cancers; such understanding can lead to preventions.