Assistant Professor, Department of Biology
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.
Many molecular machines participate in the synthesis, folding and transport of cellular proteins. We study how some of these machines function using a combination of biochemistry and single-molecule biophysics approaches. We want to learn how. The ultimate goal is to determine the mechanisms that govern protein synthesis and folding, and to understand how these processes are tuned and coordinated in the cell. This knowledge may help us to design and produce novel proteins, and to understand the mechanisms underlying protein misfolding, which is observed in a number of diseases.
Cellular proteins are synthesized by the ribosome, a very large molecular machine that decodes the genetic information and translates it into an amino acid sequence. The nascent polypeptide emerges gradually from the ribosome and is not released until synthesis is complete. We and others have shown that the ribosomal environment and the process of synthesis can affect how proteins fold. Specialized chaperones begin to interact with ribosome-bound nascent chains as they emerge during synthesis, helping them find their native structures. We are using optical tweezers, a tool to mechanically pull on single nascent polypeptides, to determine how proteins begin to fold, and how their folding is guided by the ribosome and molecular chaperones.
While virtually all proteins are synthesized in the cytosol, many of them are targeted to other cellular compartments and must cross a membrane to reach their final destination. The lipid bilayers that surround the cytosol are impermeable to proteins but contain transport systems that enable protein export. We are developing single-molecule approaches for studying the machines and processes involved the translocation of polypeptides across membranes. This will open exciting new avenues for studying membrane proteins with single-molecule biophysics approaches.
Motlagh, H.N., Toptygin, D., Kaiser, C.M. & Hilser, V.J.: Two-dimensional single-molecule force-spectroscopy provides structural access to protein folding. Biophys J 110:1280-90 (2016)
Goldman, D.H.*, Kaiser, C.M.*#, Milin, A., Righini, M., Tinoco Jr., I., and C. Bustamante. #Mechanical force releases nascent chain-mediated ribosome arrest in vitro and in vivo. Science 348: 457-60 (2015).
*equal contributions #corresponding authors
Bustamante, C., Kaiser, C.M., Maillard, A.R., Goldman, D. and C. Wilson. (2014) Mechanisms of cellular proteostasis: Insights from single molecule approaches. Annu Rev Biophys 43, 119-40.
Kaiser, C.M., P. Bujalowski, L. Ma, J. Anderson, H.F. Epstein, and A.F. Oberhauser. (2012) Tracking UNC-45 chaperone-myosin interaction with a titin mechanical reporter. Biophys. J. 102:2212-2219.
Kaiser, C.M., D. Goldman, J. Chodera, I. Tinoco, and C. Bustamante. (2011) The ribosome modulates nascent protein folding. Science 344:1723-1727.
Maillard, A.R., G. Chistol, M. Sen, M. Righini, J. Tan, C.M. Kaiser, C. Hodges, A. Martin, and C. Bustamante. (2011) ClpX generates mechanical force to unfold and translocate its protein substrates. Cell 145:459-469.
Lakshmipathy, S. K., Tomic, S., Kaiser, C. M., Chang, H. C., Genevaux, P., Georgopoulos, C., Barral, J. M., Johnson, A. E., Hartl, F. U. and S.A. Etchells. (2007) Identification of nascent chain interaction sites on trigger factor. J Biol Chem 282, 12186-93.
Kaiser, C.M., H.C. Chang, V.R. Agashe, S.K. Lakshmipathy, S.A. Etchells, M. Hayer-Hartl, F.U. Hartl, and J.M. Barral. (2006) Real-time observation of trigger factor function on translating ribosomes. Nature 444:455-460.
Pew Scholar, Class of 2015