Research in Dr. Hartl's laboratory focuses on the mechanisms of protein folding and quality control in the cell. Their long-term goal is to reach a comprehensive understanding, at the structural and functional level, of how the machinery of molecular chaperones promotes protein folding through the cooperation of co- and post-translational mechanisms. Using a range of methods from single molecule fluorescence spectroscopy to X-ray crystallography and biochemistry, they seek to decipher the rules by which the thousands of different proteins in the cytosol of bacteria and eukaryotic cells utilize the chaperone network for de novo folding and assembly. A second research focus concerns the molecular mechanisms of proteotoxicity in diseases associated with protein misfolding and aggregation. Here they wish to understand how the cellular machinery of protein homeostasis (proteostasis) normally provides protection and why these defense mechanisms increasingly fail during aging, facilitating the manifestation of neurodegenerative diseases and other disorders. In understanding the proteostasis network they are increasingly using systems-based approaches, including quantitative proteomics and genetic screens.
Saschenbrecker, S., Bracher, A., Vasudeva Rao, K., Vasudeva Rao, B., Hartl, F.U., and Hayer-Hartl, M. (2007). Structure and function of RbcX, a specific assembly chaperone for hexadecameric Rubisco. Cell 129, 1189-1200.
Sharma, S., Chakraborty, K., Müller, B.K., Astola, N., Tang, Y.-C., Lamb, D.C., Hayer-Hartl, M. and Hartl, F.U. (2008). Monitoring protein conformation along the pathway of chaperonin-assisted protein folding. Cell 133, 142-153.
Polier, S., Dragovic, Z., Hartl, F.U. and Bracher, A. (2008). Structural basis for cooperative protein folding by Hsp70 and Hsp110 molecular chaperones. Cell 133, 1068-1079.
Brandt, F., Elcock, A.H., Etchells, S.A., Ortiz, J.O., Hartl, F.U. and Baumeister, W. (2009). The native 3D topology of bacterial polysomes. Cell 136, 261-271.
Hartl, F.U. and Hayer-Hartl, M. (2009). Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol Biol. 16, 574-581.
Liu, C., Young, A.L, Starling-Windhof, A., Bracher, A., Saschenbrecker, S., Vasudeva Rao, B., Vasudeva Rao, K., Berninghausen, O., Mielke, T., Hartl, F.U. Beckmann, R. and Hayer-Hartl, M. (2010). Coupled chaperone action in folding and assembly of hexadecameric Rubisco. Nature 463, 197-202.
Chakraborty, K., Chatila, M., Sinha, J., Shi, Q., Poschner, B.C., Sikor, M., Jiang, G., Lamb, D.C., Hartl, F.U., and Hayer-Hartl, M. (2010). Chaperonin-catalyzed rescue of entropically trapped states in protein folding. Cell 142, 112-122.
Olzscha, H., Schermann, S.M., Woerner, A.C., Pinkert, S., Hecht, M.H., Tartaglia, G.G., Vendruscolo, M., Hayer-Hartl, M., Hartl, F.U., and Vabulas, R.M. (2011). Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144, 67-78.
Hartl, F.U., Bracher, A., und Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332.
Gupta, R., Kasturi, P., Bracher, A., Loew, Ch., Zheng, M., Villella, A., Garza, D., und Hartl, F.U. (2011). Firefly luciferase mutants as sensors of proteome stress. Nature Methods 8, 879-884.
Bracher, A., Starling-Windhof, A., Hartl, F.U., und Hayer-Hartl, M. (2011). Crystal structure of a chaperone-bound assembly intermediate of form I Rubisco. Nature Struct Mol Biol. 17, 875-880.
Müller-Cajar, O., Stotz, M., Wendler, P., Hartl, F.U., Bracher, A., Hayer-Hartl, M. (2011). Structure and function of the AAA+ protein CbbX, a red-type Rubisco activase. Nature 479, 194-199.
Stotz, M., Mueller-Cajar, O., Ciniawsky, S., Wendler, P., Hartl, F.U., Bracher, A., Hayer-Hartl, M. (2011). Structure of green-type Rubisco activase from tobacco. Nature Struct Mol Biol. 18, 1366-1370.