Medicine, ITESM, Monterrey, Mexico, 1995
Doctor of Philosophy, Baylor College of Medicine, Houston, Texas, 2001
Post-doctoral, Max Planck Institute of Biochemistry, Germany, 2001-2005
Prof. John J. Trentin Award, Baylor College of Medicine
Harold M. Weintraub Award, Fred Hutchinson Cancer Research Center
Pew Scholar, Pew Scholars Program in the Biomedical Sciences
Basil O'Connor Scholar, March of Dimes Foundation
About the Lab
Protein Folding in Health and Disease
To become biologically active, the great majority of proteins must acquire precise three dimensional structures. This process, known as "protein folding", depends on assistance from molecular chaperones and has been recognized to be of considerable medical and biotechnological relevance.
A number of human diseases are known to result, directly or indirectly, from aberrant protein folding reactions. In addition to loosing their normal function, misfolded polypeptides may form toxic species, may exert dominant negative effects, or may not reach their proper cellular location. Recently, a direct involvement of molecular chaperones in human disorders has become increasingly evident. A major area of research in my laboratory is to study proteins with similarities to molecular chaperones that, when mutated, lead to neurodegenerative disorders.
Expression of eukaryotic proteins in bacterial hosts often results in misfolding and aggregation, which has placed great limitations on their recombinant production. Another area of my research focuses on the mechanisms underlying the inability of the bacterial cytosol to support efficient folding of eukaryotic multi-domain proteins. We have found that bacteria and eukaryotes utilize markedly different pathways for de novo protein folding, and have begun to identify the molecules involved in these processes.
Barral, J.M., Hutagalung, A.H., Brinker, A., Hartl, F.U. and Epstein, H.F. (2002) Role of the myosin assembly protein UNC-45 as a molecular chaperone for myosin. Science 295: 669-671.
Price, M.G., Landsverk, M.L., Barral, J.M. and Epstein, H.F. (2002) Two mammalian UNC-45 isoforms are related to distinct cytoskeletal and muscle-specific functions. J. Cell Sci. 115: 4013-4023.
Young, J.C., Barral, J.M. and Hartl, F.U. (2003) More than folding: localized functions of cytosolic chaperones. Trends Biochem. Sci. 28:541-547.
Barral, J.M., Broadley, S.A., Schaffar, G. and Hartl, F.U. (2004) Roles of molecular chaperones in protein misfolding diseases. Semin. Cell Dev. Biol. 15:17-29.
Agashe, V.R., Guha, S., Chang, H.-C., Genevaux, P., Hayer-Hartl, M., Stemp, M., Georgopoulos, C., Hartl, F.U. and Barral, J.M. (2004) Function of trigger factor and DnaK in multi-domain protein folding: Increase in yield at the expense of folding speed. Cell 117:199-209.
Hoppe, T., Cassata, G., Barral, J.M., Springer, W., Hutagalung, A.H., Epstein, H.F. and Baumeister, R. (2004) Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. Cell 118:337-349.
Stemp, M.J., Guha, S., Hartl, F.U. and Barral, J.M. (2005) Efficient folding of actin in a bacterial lysate supplemented with the eukaryotic chaperonin TRiC. Biol. Chem. 386:753-757.
Chang, H.C., Kaiser, C.M., Hartl, F.U. and Barral, J.M. (2005) De novo folding of GFP fusion proteins: high efficiency in eukaryotes but not in bacteria. J. Mol. Biol. 353:397-409.
Kaiser, C.M., Chang, H.C., Agashe, V.R., Lakshmipathy,
S.K., Etchells, S., Hayer-Hartl, M., Hartl, F.U. and Barral,
J.M. (2006) Real time observation of trigger factor function
on translating ribosomes. Nature 444:455-460.
Commentary by Ada Yonath in Nature 444:435-436 (2006).
Commentary in Cell 127:653 (2006).
Commentary in Nat. Struct. Mol. Biol. 13:956 (2006).
Sealy Center for Structural Biology & Molecular Biophysics