In addition to a plethora of synthetic compounds, microtubules can interact with a wide range of structurally unrelated proteins, some of which play a role in the modulation of polymer dynamics. For instance, many Microtubule-associated proteins (MAPs) are implicated in stabilizing microtubules (e.g., XMAP215 homologues such as ZYG-9 bind to microtubules and cause them to grow longer). Conversely, some proteins induce microtubule depolymerzation (e.g., kinesin-13 proteins such as MCAK in humans and KLP-7 in worms), while others, such as katanin, sever microtubules.
microtubule dynamics because morphological changes to the cytoskeleton occur rapidly (Fig.1), and many regulatory molecules are likely required to modulate these changes.
Figure1. Within a short time-span, the C. elegans one-cell embryo displays remarkable changes in the microtubule cytoskeleton (red). The left image is an embryo at the end of meiosis. The acentrosomal meiotic spindle is near the inner left cortex. The right image shows the first mitotic spindle, with two centrosome-nucleated microtubules asters. DNA is in blue.
Using a combination of classical genetics-based suppressor/enhancer screens, RNAi and molecular biology, our goal is to identify new genes that modulate microtubule behaviour. Once identified, the genes will be characterized with respect to their effect on microtubule growth properties using traditional molecular and cell biology approaches, as well as microscopy-based assays that we will continue to develop.