In recent years, due to contributions from numerous research groups, single-molecule experiments have changed the way many biological problems are addressed. Knowledge from these experiments continues to emerge. Dr. Xiaoliang Sunney Xie’s group, Department of Chemistry, Harvard, is one of the first to pioneer fluorescence studies of single molecules at room temperature in early 1990s and has since made important advances in single-molecule enzymology and protein conformational dynamics. Dr. Xie’s work has been credited not only for bringing about technological innovations, but also for generating new insights on important scientific issues.
There are many reasons to use the single-molecule approach in biology. The most important is that single molecule experiments generate movies of motions and biochemical reactions of macromolecular machineries, which are particularly helpful in elucidating their mechanisms. Along this line, Dr. Xie is also studying nucleic acid enzymatic systems, including DNA replication and repair machineries with Dr. Xie’s collaborators.
Recently Dr. Xie’s group has taken the single-molecule experiment to live cells and have begun real-time imaging of gene expression, both at the transcriptional and translational level. To do so, Dr. Xie is developing specific, highly sensitive chemical and biochemical probes. Dr. Xie’s most recent work shows images of a protein being generated or degraded one molecule at a time in live cells. This opens up exciting possibilities for real-time gene expression profiling and system-wide study of gene regulation. Finally, Dr. Xie’s group continues to push for state-of-the-art techniques for imaging intracellular dynamics. Dr. Xie’s group has made advances in coherent anti-Stokes Raman scattering (CARS) microscopy, which allows imaging of live cells based on vibrational spectroscopy without any fluorophores. This led to the vivid observation of active transport by molecular motors in live cells such as neurons, and noninvasive imaging of live tissue at the video rate with potential medical applications.
2008 Fellow of the American Physical Society
2008 Berthold Leibinger Zukunftspreis for Laser Technology
2008 Elected to the American Academy of Arts and Sciences
2007 Willis E. Lamb Award for Laser Science and Quantum Optics
2006 Fellow of the American Association for the Advancement of Science
2006 Fellow of Biophysical Society
2004 NIH Director's Pioneer Award Recipient
2003 Raymond and Beverly Sackler Prize in the Physical Sciences, Israel
2003 Co-recipient of Hoope's Prize for Joe Markson's Outstanding Harvard undergraduate thesis
1996 Coblentz Award, Coblentz Society
1988 Jane Hart Memorial Award, University of California at San Diego
Dr. Xie's Research Group Link
Dr. Xie's Recent Publications:
Min, Wei; Lu, Sijia; Holtom, Gary R.; Xie, X. Sunney "Triple-Resonance Coherent Anti-Stokes Raman Scattering Microspectroscopy," ChemPhysChem, 10, 344-347 (2009).
Murugkar, S.;Evans, C.L.; Xie, X.S.; Anis, H. "Chemically specific imaging of cryptosporidium oocysts using coherent anti-Stokes Raman scattering (CARS) microscopy," Journal of Microscopy, 233, 244-250 (2009).
Freudiger, Christian W.; Min, Wei; Saar, Brian G.; Lu, Sijia; Holtom, Gary R.; He, Chengwei; Tsai, Jason C; Kang, Jing X.; Xie, X. Sunney "Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy," Science, 322, 1857-1861 (2008)
Choi, Paul J.; Cai, Long; Frieda, Kirsten; Xie, X. Sunney "A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell," Science, 322, 442-446 (2008).
Xie, X. Sunney; Choi, Paul J.; Li, Gene-Wei; Lee, Nam Ki; Lia, Giuseppe "Single-Molecule Approach to Molecular Biology in Living Bacterial Cells," Annu. Rev. Biophys, 37, 417-444 (2008).
Evans, Conor; Xie, X. Sunney "Coherent Anti-Stokes Raman Scattering Microscopy: Chemical Imaging for Biology and Medicine," Annu. Rev. Anal. Chem., 1, 883-909 (2008).
Potma, Eric O.; Xie, X. Sunney "Coherent Anti-Stokes Raman Scattering (CARS) Microscopy: Instrumentation and Applications" in "Handbook of Biomedical Nonlinear Optical Microscopy" Edited by Barry R. Masters and Peter T.C. So, p 164-186, Oxford University Press, New York, New York (2008).
Potma, Eric O.; Xie, X. Sunney "Theory of Spontaneous and Coherent Raman Scattering" in "Handbook of Biomedical Nonlinear Optical Microscopy" Edited by Barry R. Masters and Peter T.C. So, p 164-186, Oxford University Press, New York, New York (2008).
Nan, Xiaolin; Sims, Peter A.; Xie, X. Sunney "Organelle Tracking in a Living Cell with Microsecond Time Resolution and Nanometer Spatial Precision," ChemPhysChem, 9, 707-712 (2008).
Li, Jianwei Jeffery; Chu, Yizhuo; Lee, Benjamin Yi-Hung; Xie, X. Sunney "Enzymatic signal amplification of molecular beacons for sensitive DNA detection," Nucleic Acids Research, 1-17 (2008).
Min, Wei; Xie, X. Sunney; Bagchi, Biman "Two-Dimensional Reaction Free Energy Surfaces of Catalytic Reaction: Effects of Protein Conformational Dynamics on Enzyme Catalysis," J.Phys.Chem.B, 112, 454-466 (2008).
Xiao, Jie; Elf, Johan; Li, Gene-Wei; Yu, Ji; Xie, S. Sunney "Imaging Gene Expression in Living Cells at the Single-Molecule Level" in "Single-Molecule Techniques A Laboratory Manual" Edited by Paul R. Selvin and Taekjip Ha, p 149-170, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2008.
Schroeder, Charles M.; Blainey, Paul C.; Kim, Sangjin; Xie, X. Sunney "Hydrodynamic Flow-stretching Assay for Single-Molecule Studies of Nucleic Acid-Protein Interactions" in "Single Molecule Techniques A Laboratory Manual" Edited by Paul R. Selvin and Taekjip Ha, p 461-492, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2008.
Wright, A.J.; Poland, S.P.; Girkin, J.M.; Freudiger, C.W.; Evans, C.L.; Xie, X.S. "Adaptive Optics for enhanced signal in CARS microscopy," Optics Express, 15, 18209-18219 (2007).
Saar, Brian G.; Park, Heung-Shik; Xie, X. Sunney; Lavrentovich, Oleg D. " Three-dimensional imaging of chemical bond orientation in liquid crystals by coherent anti-Stokes Raman scattering microscopy," Optics Express, 15, 13585-13596 (2007).
Evans, Conor L.; Xu, Xiaoyin; Kesari, Santosh; Xie, X. Sunney; Wong, Stephen T.C.; Young, Geoffrey S. "Chemically-selective Imaging of Brain Structures with CARS Microscopy," Optics Express, 15, 12076-12087 (2007).
Luo, Guobin; Wang, Mina; Konigsberg, William H.; Xie, X. Sunney "Single-molecule and ensemble fluorescence assays for a functionally important conformational change in T7 DNA polymerase," PNAS, 104, 12610-12615 (2007).
Kim, Sangjin; Blainey, Paul C; Schroeder, Charles M; Xie, X. Sunney "Multiplexed single-molecule assay for enzymatic activity on flow-stretched DNA," Nature Methods, 4, 397-399 (2007).
Elf, Johan; Li, Gene-Wei; Xie, X. Sunney "Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell," Science, 316, 1191-1194 (2007).
Friedman, Nir; Cai, Long; Xie, X. Sunney "Linking Stochastic Dynamics to Population Distribution: An Analytical Framework of Gene Expression," Phys. Rev. Lett. 97, 168302 (2006).
Min, Wei; Gopich, Irina V.; English, Brian P.; Kou, Sam C.; Xie, X. Sunney.; Szabo, Attila "When Does the Michaelis-Menten Equation Hold for Fluctuating Enzymes?" J. Phys. Chem. B, 110, 20093-7 (2006).
Xie, X. Sunney; Cheng, Ji-Xin; Potma, Eric O. "Coherent Anti-Stokes Raman Scattering Microscopy" in "Handbook of Biological Confocal Microscopy" 3rd ed. Edited by James Pawley, p 595-606, Springer Science, New York, 2006.
Qian, Hong; Xie, X. Sunney "Generalized Haldane Equation and Fluctuation Theorem in The Steady-state Cycle Kinetics of Single enzymes," Phys. Rev. E, 74, 010902(R) (2006).
Nan, Xiaolin; Potma, Eric O.; Xie, X. Sunney "Nonperturbative Chemical Imaging of Organelle Transport in Living Cells with Coherent anti-Stokes Raman Scattering Microscopy," Biophys. J., 91, 728-735 (2006)
Luo, Guobin; Andricioaei, Ioan; Xie, X. Sunney; Karplus, Martin "Dynamic Distance Disorder in Proteins Is Caused by Trapping," J. Phys. Chem. B, 110, 9363-9367 (2006).
Ganikhanov, Feruz; Evans, Conor L.; Saar, Brian G.; Xie, X. Sunney "High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy," Optics Lett., 31, 1872-1874 (2006).
Légaré, François; Evans, Conor L.; Ganikhanov, Feruz; Xie, X. Sunney "Towards CARS Endoscopy," Opt. Express,14 , 4427-4432 (2006).
Ganikhanov, Feruz; Carrasco, Silvia; Xie, X. Sunney; Katz, Mordechai; Seitz, Wolfgang; Kopf, Daniel "Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy," Optics Lett., 31, 1292-1294 (2006).
Xie, X. Sunney; Yu, Ji; Yang, Wei Yuan "Living Cells as Test Tubes," Science, 312, 228-230 (2006).
Blainey, Paul C.; van Oijen, Antoine M.; Banerjee, Anirban; Verdine, Gregory L.; Xie, X. Sunney "A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA," Proc. Natl. Aca. Sci., 103, 5752-5757 (2006).
Lee, Jong-Bong; Hite, Richard K.; Hamdan, Samir M.; Xie, X. Sunney; Richardson, Charles C.; van Oijen, Antoine M. "DNA primase acts as a molecular brake in DNA replication," Nature, 439, 621-624 (2006).
Rakic, Bojana; Noestheden, Matthew; Belanger, Sylvie; Nan, Xiaolin; Evans, Conor L.; Xie, X. Sunney; Pezacki, John Paul "Peroxisome Proliferator-Activated Receptor Alpha Antagonism Inhibits Hepatitis C Virus Replication Source," Chemistry and Biology, 13, 1-8 (2006).
Yu, Ji; Xiao, Jie; Ren, Xiaojia; Lao, Kaiqin; Xie, X. Sunney; "Probing Gene Expression in Live Cells, One Protein Molecule at a Time," Science, 311, 1600-1603 (2006).
Cai, Long; Friedman, Nir; Xie, X. Sunney "Stochastic protein expression in individual cells at the single molecule level," Nature, 440, 358-362 (2006).
Min, Wei; Xie, X. Sunney "Kramers model with a power-law friction kernel: Dispersed kinetics and dynamic disorder of biochemical reactions," Phys. Rev. E 73, 010902 (2006).
English, Brian P.; Min, Wei; van Oijen, Antoine M.; Lee, Kang Taek; Luo, Guobin; Sun, Hongye; Cherayil, Binny J.; Kou, S.C.; Xie, X. Sunney "Ever-fluctuating single enzyme molecules: Michaelis-Menten equation revisited," Nat. Chem. Bio., 2, 87 (2006).
Potma, Eric O.; Evans, Conor L.; Xie, X. Sunney "Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging," Optics Lett. 31, 241 (2006).