Research Group BOXEM

Cell polarization is critical to animal development and tissue functioning, and defects in polarity are an important factor in the development of cancer and other diseases. We study the molecular mechanisms that underlie cell polarity using a combination of high-throughput protein interaction mapping approaches and in vivo studies using the model organism C. elegans.

Protein-protein interactions are a key component of any biological process. With the recent availability of genomic sequences for various organisms, it is now possible to identify these interactions systematically on a large scale, predominantly using the yeast two-hybrid system or affinity purification followed by mass spectrometry. Current genome-wide protein interaction maps are still far from complete and often lack important information needed to elucidate complex processes, such as the protein domains that mediate interactions, and the tissue-specific nature of interactions. We recently developed a yeast two-hybrid approach to systematically identify interaction domains, and are developing affinity purification strategies to examine tissue-specific differences in the composition of protein complexes. We are using these approaches to identify the molecular interactions and protein complexes involved in cell polarization in C. elegans.

To test novel hypotheses and candidate polarity proteins derived from the interactions identified, we make use of several polarity models available for C. elegans. Polarity of embryonic and post-embryonic tissues can be examined in live animals using fluorescently labeled proteins that are asymmetrically distributed or visualize components such as membranes, cell junctions, or the mitotic spindle. In combination with gene inactivation by RNA interference or mutations, these models allow us to examine the role of individual proteins in cell polarity in the context of a living, multicellular organism.