Patrick Barth, Ph.D.
Department of Pharmacology
Department of Biochemistry & Molecular Biology
Education and Awards
- Ph.D., University of Paris XI, France
- Postdoctoral, University of California, Berkeley and University of Washington
Exploring signaling mechanisms across biological membranes using integrative computational / experimental approaches
My lab is interested in how signals are faithfully transmitted across biological membranes. How do receptors sense and respond to diverse ligands? How do receptors communicate with each other in the membrane? How do receptor-receptor interactions modulate signaling? Can we recapitulate these properties by design and rewire signaling pathways?
We address these questions using a combination of molecular modeling, bioinformatics and experimental approaches to model, design and reprogram receptor/ligand interaction networks. Our long-term goal is to deconstruct the complex function and quantitatively describe the basic principles underlying these signaling networks.
We have developed an ensemble of physical models and computational methods to model and design receptor structures and interactions. We have also combined experimental data with modeling techniques to model specific functional states of receptors. Finally, we have cross-validated our predictions experimentally. This interdisciplinary approach is essential to our research and we welcome students and postdocs with computational and experimental backgrounds to continue fostering a very collaborative environment in the lab.
Selected Publications: (* these authors contributed equally)
- Michino, M., et al. Community-wide assessment of GPCR structure modelling and ligand docking : GPCR Dock 2008 (2009) Nature Review Drug Discovery 8(6), 455-63. [PubMed]
- Barth, P.*, Zhu, J.*, Luo, B.H.*, Schonbrun, J., Baker, D., Springer, T. The structure of a receptor with two associating transmembrane domains on the cell surface : integrin aIIbb3. (2009) Molecular Cell 34(2), 234-49. [PubMed]
- Barth, P.*, Wallner, B.*, Baker, D. Prediction of membrane protein structures with complex topologies using limited constraints. (2009) Proc Natl Acad Sci U S A (Track II) 106(5), 1409-14. [PubMed]
- Barth, P., Schoeffler, A., Alber, T. Targeting metatstable coiled-coil domains by computational design (2008) Journal of the American Chemical Society, 130(36), 12038-44. [PubMed]
- Barth, P. Modulating membrane protein stability and association by design (2007) Current Opinion in Structural Biology 17(4), 460-466. [PubMed]
- Pathak, M.*, Yarov-Yarovoy, V.*, Agarwal, G., Roux, B., Barth, P., Kohout, S., Tombola, F., Isacoff , E.U. Closing in on the resting state of the shaker K+ channel (2007) Neuron 56(1), 124-140. [PubMed]
- Barth, P., Schonbrun, J., Baker D. Toward high-resolution prediction and design of transmembrane helical protein structures (2007) Proc Natl Acad Sci U S A (Track II) 104(40), 15682-15687. [PubMed]
- Barth, P., Alber, T., Harbury, P.B. Accurate, conformation-dependent predictions of solvent effects on protein ionization constants (2007) Proc Natl Acad Sci U S A (Track I) 104(12), 4898-903. [PubMed]