Campus Directory

Division Physical & Biological Sciences Division

Department/College/Unit Chemistry & Biochemistry Department

Title Professor

Affiliation Faculty

Faculty Type Regular Faculty

Areas of Expertise Chemistry

Web Site

Primary Office Location Physical Sciences Building
462

Additional Location(s) Physical Sciences Bldg 459 (Lab)

Mail Stop Chemistry

Biography, Education and Training

B.A. University of Pennsylvania, Philadelphia
Ph.D. UC Berkeley

Summary of Expertise

Molecular basis of telomere length and telomerase-related diseases; biophysical characterization of nucleic acid-associated molecular motors; development of novel approaches for imaging enzymes in cells

Research Interests

Single-molecule Biophysics and Enzymology; Structure, function, and assembly of the telomerase ribonucleoprotein, Fluorescence Resonance Energy Transfer (FRET), optical/magnetic trapping.

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 magnetic trapping to investigate the unique structural properties of telomere DNA and the molecular mechanisms of telomere remodeling proteins that contribute to telomerase regulation.

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

• Dynamics of nucleosome remodelling by individual ACF complexes Blosser, T.R., Yang, J.R., Stone, M.D., Narlikar, G.J., Zhuang, X. (2009). Nature 462, 1022-1027.
• Assembly of Complex RNAs by Splinted Ligation Akiyama, B.M., Stone, M.D. (2009). Methods in Enzymology. Vol. 469, 27-46.
• A single-molecule assay for telomerase structure-function analysis Wu, J.Y., Stone, M.D., Zhuang, X. (2009). Nucleic Acids Research Advance Access published on November 17, 2009.
• Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Stone, M.D., Mihalusova, M., O'Connor C, M., Prathapam, R., Collins, K., and Zhuang, X. (2007). Nature 446, 458-461.
• Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. 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). Nat Struct Mol Biol 14, 264-271.
• Mechanochemical analysis of DNA gyrase using rotor bead tracking. Gore, J., Bryant, Z., Stone, M.D., Nollmann, M., Cozzarelli, N. R., and Bustamante, C. (2006). Nature 439, 100-104.
• Structural transitions and elasticity from torque measurements on DNA. Bryant, Z., Stone, M.D., Gore, J., Smith, S. B., Cozzarelli, N. R., and Bustamante, C. (2003). Nature 424, 338-341.
• Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Stone, M.D., Bryant, Z., Crisona, N. J., Smith, S. B., Vologodskii, A., Bustamante, C., and Cozzarelli, N. R. (2003). Proc Natl Acad Sci U S A 100, 8654-8659.