Over the course of evolution, organisms have developed variations in their cell cycle programs to be able to generate and maintain a plethora of different cell types and tissues. Our lab uses a variety of model systems, such as the nematode C. elegans, as well as in vitro culture systems, to address fundamental questions in cell cycle control during development and tissue formation. Current projects include:
Mitotic checkpoint signaling in different cell types
Antimitotic drugs, such as the microtubule poisons taxanes and vinca alkaloids, are widely used as chemotherapeutics for cancer treatment. These agents disrupt the microtubule cytoskeleton, thereby inhibiting the attachment of chromosomes to the mitotic spindle and activating the spindle assembly checkpoint (SAC), a surveillance mechanism that delays the progression of cell division. Very little is known on SAC signaling in normal tissues in vivo, and whether distinct cell types exhibit differences in SAC activation. Our recent analysis of SAC signaling in C. elegans revealed that there is a gradual increase in SAC strength during early embryogenesis, as cells become smaller and smaller (Galli and Morgan, 2016). We are currently studying how cell size controls SAC strength, and whether different tissues have different SAC activities.
Polyploidy in development and disease
Although most animal species are diploid, many tissues and cell types within animals are polyploid, i.e. they contain more than two copies of their DNA. Polyploidy can arise by cell fusion, or alternatively, by endoreplication or endomitosis, two cell cycle alterations that lead to the replication of DNA without cell division. It is currently largely unclear how cells initiate these alternative cell cycles, and what their functional importance is for tissue homeostasis. Moreover, polyploidization is also often observed under pathological conditions, as it can arise as a response to stress or cell division failures. Our lab is interested in understanding how polyploidization is regulated in normal physiology and what the functional consequences are of becoming polyploid for cells and tissues. To address these questions, we have established a variety of different in vitro and in vivo cell systems that allow us to dissect molecular mechanisms and function.