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Chemistry and Biochemistry
University of California
230 Physical Sciences Bldg.
Santa Cruz, CA 95064
Phone: (831) 459-4002
Fax: (831) 459-2935
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Michael Stone Assistant Professor of Chemistry & Biochemistry BA University of Pennsylvania, Philadelphia Ph.D. UC Berkeley Office: PSB 260 Phone: (831) 459-2845 Fax: (831) 459-2935 mstone@chemistry.ucsc.edu Web: www.stone.chemistry.ucsc.edu

Stone Research Group Department of Chemistry University of California 1156 High Street Santa Cruz, CA 95064 Office Hours Class Times and Locations Labs:

RESEARCH INTERESTS: Single-molecule Biophysics and Enzymology; Structure, function, and assembly of the telomerase ribonucleoprotein, Fluorescence Resonance Energy Transfer (FRET), optical/magnetic trapping, sub-diffraction optical imaging of telomeres and the nucleus.

     Telomeres are specialized chromatin structures that prevent deleterious chromosome fusion events by differentiating normal chromosome ends from sites of DNA damage. Telomere DNA is synthesized by the telomerase ribonucleoprotein (RNP), an enzyme comprised of the telomerase reverse transcriptase, telomerase RNA, and several additional protein cofactors. Telomerase activation is a tightly regulated process restricted to rapidly dividing cell types such as stem cells and the majority of human tumors. It is thus of direct medical importance to understand fundamental mechanisms governing telomerase assembly and function.
      My laboratory takes a multi-disciplinary approach to study the structure and function of telomerase, combining established biochemical methods with emerging single molecule techniques which allow direct analysis of complex dynamics not possible with traditional ensemble measurements. For example, we employ single molecule fluorescence resonance energy transfer (smFRET) to monitor telomerase structure and dynamics during RNP assembly and catalysis. In addition, we utilize micro-manipulation techniques such as optical and magnetic trapping to investigate the unique structural properties of telomere DNA and the molecular mechanisms of telomere remodeling proteins that contribute to telomerase regulation. Other projects include the use of sub-diffraction in vivo optical microscopy to investigate the nuclear organization of telomeres, telomerase RNP components, and sub-nuclear organelles implicated in telomerase assembly.
     Students in my laboratory will have the opportunity to participate in diverse areas of research including: molecular biology, protein and nucleic acid biochemistry, design and fabrication of biophysical instrumentation, software development, and quantitative data analysis.

SELECTED PUBLICATIONS

Stone, M.D., Mihalusova, M., O'Connor C, M., Prathapam, R., Collins, K., and Zhuang, X. (2007). Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature 446, 458-461.

Nollmann, M., Stone, M.D., Bryant, Z., Gore, J., Crisona, N. J., Hong, S. C., Mitelheiser, S., Maxwell, A., Bustamante, C., and Cozzarelli, N. R. (2007). Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. Nat Struct Mol Biol 14, 264-271.

Gore, J., Bryant, Z., Stone, M.D., Nollmann, M., Cozzarelli, N. R., and Bustamante, C. (2006). Mechanochemical analysis of DNA gyrase using rotor bead tracking. Nature 439, 100-104.

Stone, M.D., Bryant, Z., Crisona, N. J., Smith, S. B., Vologodskii, A., Bustamante, C., and Cozzarelli, N. R. (2003). Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Proc Natl Acad Sci U S A 100, 8654-8659.

Bryant, Z., Stone, M.D., Gore, J., Smith, S. B., Cozzarelli, N. R., and Bustamante, C. (2003). Structural transitions and elasticity from torque measurements on DNA. Nature 424, 338-341.