Dr. Berger received his Ph.D. in Biochemistry at the University of Minnesota in 1991, and continued his research examining the molecular mechanism of muscle contraction as a post-doctoral associate at the University of Pennsylvania. He joined the University of Vermont as an assistant professor of Molecular Physiology & Biophysics in 1994, was promoted to the rank of Associate Professor in 2000, and has had a secondary appointment in the Department of Biochemistry since 1996. Dr. Berger has been a member of the CMB Program since 1994 served as the Program's Director from 2003-2006, and currently serves on the Education Committee.

Research Interests

Currently, Dr. Berger's lab is using state-of-the-art techniques in molecular biology and fluorescence spectrosocpy to elucidate the structural changes in molecular motor proteins responsible for a variety of cellular processes including muscle contraction, organelle transport, and chromosome segregation during mitosis.

The majority of our research has focused on myosin, which functions to produce force and motion during muscle contraction and other forms of cell motility. Conformational changes within myosin at critical steps of the contractile cycle are examined using mutants of the smooth muscle myosin motor domain genetically engineered by site-directed mutagenesis to contain a single tryptophan residue and expressed in a baculovirus/sf9 cell culture system. Structural alterations in response nucleotide-binding, ATP hydrolysis, and actin binding are assessed using a variety of spectroscopic techniques to examine the intrinsic fluorescence from the single tryptophan residue in question, including steady-state and lifetime decay emission, acrylamide quenching, time-resolved anisotropy, and fluorescence resonance energy transfer. These experiments allow information about the environment around each tryptophan, including polarity, accessibility, restriction of motion, and distance to other intramolecular sites to be obtained at specific steps of the contractile cycle. Stopped-flow fluorescence measurements are also made to correlate specific structural changes in myosin with the kinetics of individual steps in the chemical ATPase cycle. These methods are currently being expanded to examine similar structure/function relationships in kinesin, a molecular motor involved in both organelle transport within in the cell and chromosome segregation during mitosis.

Functional domains of myosin, a molecular motor protein.

Selected Publications

Robertson, C.I., Gaffney, D.P., Chrin, L.R., and Berger, C.L. Structural Rearrangements in the Active Site of Smooth-Muscle Myosin. Biophys J. 2005 Sep;89(3):1882-92

Yengo, C.M., De La Cruz, E.M., Chrin, L.R., Gaffney, D.P. and Berger, C.L. Actin-induced closure of the actin-binding cleft of smooth muscle myosin. J Biol Chem. 2002 Jul 5;277(27):24114-9

van Duffelen, M., Chrin, L.R., and Berger, C.L. Kinetics of structural changes in the relay loop and SH3 domain of myosin. Biochem Biophys Res Commun. 2005 Apr 8;329(2): 563-72

van Duffelen, M., Chrin, L.R. and Berger, C.L. Nucleotide dependent intrinsic fluorescence changes of W29 and W36 in smooth muscle myosin. Biophys J 2004 87(3):1767-1775

Yengo, C.M., Chrin, L.R., Rovner, A.S. and Berger, C.L. Tryptophan 512 is sensitive to conformational changes in the rigid relay loop of smooth muscle myosin during the MgATPase cycle. J Biol Chem. 2000 Aug 18;275(33):25481-7

CMB Lab Members