Our focus lies in understanding the downstream events of ciliary bending, namely
The mTOR pathway is the major regulator of cell size and upregulated in polycystic kidney diesease (PKD). We recently established a link between ciliary bending in response to flow and mTOR inhibition (Boehlke et al., 2010). Cilia dysfunction in a murine mouse model and cell culture experiments led to failure of mTOR inhibition and subsequently to upregulation of cell size. Lkb1, the mutated gene in Peutz-Jeghers-Syndrome, and its downstream target AMPK are localized within the ciliary-basal body compartment governing cell size control in vitro. In the future we plan to further elucidate the downstream targets of Lkb1-AMPK signaling and clarify the interplay of polycystins and cilia in mTOR control.
One other focus of our group is to understand how cilia influence polarisation decisions within the epithelial plane (planar cell polarity). Epithelial cells cultivated in our flow chamber system show centriole movements in the direction of flow which depend on polycystin 2 (Kotsis et al., 2008). We are in the process to unravel the downstream targets of flow-dependent centriole movements.
We utilize state of the art biomolecular methods and several life imaging techniques including a sophisticated flow chamber system in constant collaboration with Roland Nitschke at the Live Imaging Center (LIC, Center for Biological Systems Analysis, Freiburg).