Christian Kaiser joined the Department of Biology in 2013 as assistant professor. He holds a joint appointment in the Department of Biophysics, as well as in the Johns Hopkins University School of Medicine Department of Biophysics and Biophysical Chemistry. Prior to coming to Hopkins, he did postdoctoral work at the University of Texas Medical Branch at Galveston, and the University of California, Berkeley.
Our lab is interested in learning how cells make and maintain functional proteins. Protein biogenesis involves a variety of processes: Translation of the genetic code by the ribosome, targeting of the translation product to the proper cellular location, and folding into its native structure, often aided by molecular chaperones. We want to understand—at a mechanistic level—the molecular machines that synthesize, transport, and fold proteins. Knowing the molecular mechanisms will help us understand how these processes are tuned and synchronized.
We use optical tweezers to watch and manipulate the molecular machines involved in protein biogenesis. This single molecule approach helps us to overcome some of the challenges associated with studying these machines and the processes they carry out. Using reconstituted components, we are studying how the ribosome and the nascent chain interact with each other, how molecular chaperones affect protein folding and structural maintenance, and how the translocon helps polypeptides cross membranes and become functional. Ultimately, this will enable us to understand how cells obtain and maintain a functional proteome.
Chang, H. C., Kaiser, C. M., Hartl, F. U. & Barral, J. M.: De novo folding of GFP fusion proteins: high efficiency in eukaryotes but not in bacteria. J Mol Biol 353, 397-409 (2005).
Kaiser, C. M., Chang, H. C., Agashe, V. R., Lakshmipathy, S. K., Etchells, S. A., Hayer-Hartl, M., Hartl, F. U. & Barral, J. M.: Real-time observation of trigger factor function on translating ribosomes. Nature444, 455-60 (2006). (Commentary by Ada Yonath in Nature 444, 435-436; 2006.)
Lakshmipathy, S. K., Tomic, S., Kaiser, C. M., Chang, H. C., Genevaux, P., Georgopoulos, C., Barral, J. M., Johnson, A. E., Hartl, F. U. & Etchells, S. A.: Identification of nascent chain interaction sites on trigger factor. J Biol Chem 282, 12186-93 (2007).
Maillard, A.R., Chistol, G., Sen, M., Righini, M., Tan, J., Kaiser, C.M., Hodges, C., Martin, A. & Bustamante, C.: ClpX Generates Mechanical Force to Unfold and Translocate its Protein Substrates. Cell145, 459-469 (2011)
Kaiser, C.M., Goldman, D., Chodera, J., Tinoco, I. & Bustamante, C.: The ribosome modulates nascent protein folding. Science 344, 1723-7 (2011)
Kaiser, C.M., Bujalowski, P., Ma, L., Anderson, J., Epstein, H.F., and Oberhauser, A.F.: Tracking UNC-45 Chaperone-Myosin Interaction with a Titin Mechanical Reporter. Biophys J 102, 2212 9 (2012)
Yu-Chi (Kiki) Chang