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:
Cell-cycle control during multicellular development
Most of our knowledge on cell-cycle control stems from studies performed in unicellular systems, such as yeast or mammalian cells in culture, and we know surprisingly little on how cell cycles are controlled within the context of a multicellular organism. This is particularly important, because within an animal, not all cells are equal, and cellular differentiation has a profound impact on the cell cycle. For example, different cell types can cycle at different speeds, their cell-cycle checkpoints can have different strengths, they can permanently arrest or exit the cell cycle, or they can transition to non-canonical cell cycles, thereby skipping specific phases of the canonical cell cycle. In our lab we study the intestinal lineage of C. elegans as a model system to understand how cell-cycle changes are orchestrated during cellular differentiation. In this system, intestinal cells sequentially transition through three distinguishable cell cycles during defined moments in development, and we are using a variety of microscopy and RNA sequencing techniques to identify novel regulators of cell-cycle switching.
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.