Primary cilia are basically signaling hubs, harboring amongst others the noncanonical WNT, Hedgehog,and PDGF signaling systems, and their disruption leads to striking developmental defects. Some ciliopathy-associated proteins have recently been revealed to be physically or functionally associated in several distinct groupings, with limited connections to other crucial biological processes. Early proteomics studies have also suggested a discrete repertoire of about 1000 proteins within the organelle (i.e. <5% of the proteome) that are still in need of organisation into pathways and networks. Small, relatively isolated systems are often targeted by systems biology approaches under the assumption that a limited set of molecules and interactions will be more tractable for modelling systems. Cilia are thus ideal organelles for systems biology as they can be regarded as semi-closed systems being both largely spatially and biologically separated from many other cellular structures and processes.
Scientific and technical objectives
Our overall objectives are to establish a paradigm for studying and modelling complex eukaryotic systems, to understand how system perturbation contributes to the modulation of clinical phenotypes, and to provide a better understanding of ciliary processes in biology and their associated diseases. Our objectives focus on all critical components of the systems biology process, namely:
• assay development and application
• data generation, handling and integration
• model building and testing followed by refinement.
We also exploit the models to find new insights into biological mechanism and human disease, and to develop approaches for ciliotherapies.