Cytoskeletal control of cell shape
The overarching goal of the Tyska Laboratory is to understand how transporting epithelial cells assemble a functional apical surface. Intestinal epithelial cells in particular build one of the most elaborate apical specializations, an array of microvilli known as the brush border. Our current studies are investigating how enterocytes assemble this domain, how the brush border contributes to maintaining physiological homeostasis, and how perturbation of this interface by inherited or infectious causes leads to human disease. Over the past decade, the Tyska Laboratory has made a number of fundamental and field-leading discoveries on the assembly and function of the brush border interface. During this time, our research program has evolved an approach that combines elements of biochemistry, physiology, biophysics, and cell biology. Although light and electron microscopy serve as our principle discovery tools, our investigations are decidedly broad in scope, ranging from physiological experiments in mouse model systems, to optical trap-based measurements on single cells, to single molecule imaging in live cells. Our group has also leveraged strong collaborations with other investigators in- and outside Vanderbilt University. Importantly, the critical physiological significance of the brush border means that many of our basic science findings hold direct relevance for understanding human disease. As an example, our discovery of intermicrovillar adhesion (Crawley et al. Cell 2014; Crawley et al. Dev Cell 2016, Weck et al. Current Biology, 2016) led us to uncover the molecular basis of intestinal symptoms in patients with Type 1 Usher Syndrome.