Research

Functional proteomics in ciliary diseases

Our ongoing studies with the IFT-A complex and its interacting partners suggest that this conserved complex interacts with a set of novel effectors in mammalian cells including Tulp3.

We have generated protein interaction maps for these individual interactors. Computational analyses of the emerging graph properties (such as the connectivity and betweenness-centrality/clustering coefficients of the nodes (Seebacher and Gavin, 2011)) of this extended network help us prioritize the relative importance of these factors.

Furthermore, we have already undertaken reverse genetic approaches for dissecting the roles of some of these genes in Hh signaling. Recent studies show the remarkable importance of the IFT-A complex in causing ciliopathies (Arts et al., 2011; Ashe et al., 2012; Bredrup et al., 2011). We are currently collaborating with human genetics groups of Drs. Friedhelm Hildebrandt (University of Michigan) and Tania Attie-Bitach (INSERM) in order to utilize these extended networks in discovering novel genes important in causing ciliopathies.

References

Arts, H.H., Bongers, E.M., Mans, D.A., van Beersum, S.E., Oud, M.M., Bolat, E., Spruijt, L., Cornelissen, E.A., Schuurs-Hoeijmakers, J.H., de Leeuw, N., et al. (2011). "C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome." J Med Genet 48, 390-395.

Ashe, A., Butterfield, N.C., Town, L., Courtney, A.D., Cooper, A.N., Ferguson, C., Barry, R., Olsson, F., Liem, K.F., Jr., Parton, R.G., et al. (2012). "Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies." Hum Mol Genet.

Bredrup, C., Saunier, S., Oud, M.M., Fiskerstrand, T., Hoischen, A., Brackman, D., Leh, S.M., Midtbo, M., Filhol, E., Bole-Feysot, C., et al. (2011). "Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19." Am J Hum Genet 89, 634-643.

Seebacher, J., and Gavin, A.C. (2011). "SnapShot: Protein-protein interaction networks." Cell 144, 1000, 1000 e1001.