Dr. Mike Boxem
My group uses a combination of systems biology approaches, systematic experimental manipulation, and live-cell imaging to study the process of cell polarization. Cell polarity – the asymmetric distribution of components or functions within a cell – is a basic property of most cells that is essential in development and for the functioning of adult tissues. For example, polarity is required for the generation of different cell types through asymmetric cell divisions, and most cell types need to establish functionally distinct domains to perform their functions. Cell polarity is mediated by mutually inhibitory interactions between several groups of cortical proteins.
The most abundant polarized cell type of the animal body is the epithelial cell. Polarization of epithelial cells into apical and basolateral domains is essential for epithelia to be able to function as selectively permeable barriers. Loss of epithelial polarity contributes to epithelial diseases like polycystic kidney disease and retinal dystrophies. Moreover, epithelial cancers are characterized by loss of cell polarity and epithelial integrity, and many polarity regulators are mutated or deregulated in cancer.
Research in our group addresses three main polarity-related questions:
- What are the functional interactions that maintain polarity in existing epithelial tissues?
- What are the direct consequences of loss of polarity to the behavior and fate of cells, and how does loss of polarity predispose cells to overproliferation?
- How is cortical polarity connected with other cellular processes that contribute to cell polarity?
To address these questions, we make use of Caenorhabditis elegans as a model system. This small nematode has multiple epithelial tissues, and the proteins that control polarity are conserved between C. elegans and human. C. elegans is ideal for live observations of cell polarity due to its transparency and small number of cells. In combination with recent technological advances made possible by the use of CRISPR-based genome engineering, we can now precisely manipulate polarity in living tissues, and follow the effects on epithelial tissues and on the polarizing machinery with unprecedented detail and accuracy. Moreover, using genetic screens we can identify components that act in concert with cortical polarity regulators to establish the full polarized cell morphology.