Strathcona Anatomy & Dentistry Building, Room W-309
Dr Mandato studies cytokinesis or cell fission, which is one of the most mysterious processes of the animal cell division cycle. It has long been known that during animal cell cytokinesis a contractile ring composed of actin filaments and myosin-2 is responsible for generating the force necessary for this fission event, while microtubules are somehow responsible for directing the assembly of the contractile ring. Likewise the force needed for cellular locomotion is also generated by actin filaments and myosin-2 and somehow controlled by microtubules. However, little is known about how these two polymeric systems work together to assemble and establish localized, coordinated contractile structures. Given the significance of these cellular functions to both normal and pathological human physiology, understanding the mechanisms by which they are controlled is of clear biological and clinical importance. To examine these contractile structures Dr Mandato's Lab studies the in vivo relationship of these two polymeric systems and characterizes the molecular basis of their interactions during cellular wound healing, a process which entails rapid, microtubule-dependent assembly and closure of an actomyosin contractile ring which is ideal for experimental analysis. The goal of this research is to provide important and novel insights into the molecular mechanisms by which microtubules control actomyosin during contractile events such as cytokinesis and cellular wound healing. Biologically, this interaction is of the utmost importance. The perturbation of this interaction results in aberrant cytokinesis, which leads to aneuploidy, a condition tightly correlated with cancer aggression. Inhibition of microtubule dynamics are the mechanistic basis for the antitumor effects of most antimitotic compounds. Therefore increasing our knowledge of this basic cellular event will aid in designing more effective chemotheraputic compounds.