Microtubules are dynamic polymers that undergo phases of polymerization and depolymerization. This behaviour allows the rapid assembly and disassembly of intracellular microtubule-based structures such as the mitotic spindle, which is essential for chromosome segregation, cytokinesis and the execution of polarity signals. The importance of the microtubule
cytoskeleton to cell division is further evidenced by the fact that many anti-cancer drugs poison the polymer itself (e.g.
Taxol and Vinblastine).
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.
Many proteins contribute to the formation of microtubule-based structures in the cell, but we are still far from understanding how microtubule dynamics are regulated temporally and spatially in vivo. The one-cell C. elegans embryo is ideal for the study of
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.
microtubule dynamics because morphological changes to the cytoskeleton occur rapidly (Fig.1), and many regulatory molecules are likely required to modulate these changes.
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.