Quad Erat Demonstratum

Dr. Pam Thuman-Commike, Director of Research.

Education

Ph.D., Computational & Structural Biology, Baylor College of Medicine, 1996
Computational improvements in the determination of icosahedral virus structures using electron cryo-microscopy and structural studies of scaffolding-containing P22 procapsids.

M.S., Computer Science, University at Buffalo,1992
Parallel solutions to the phase problem in X-ray crystallography.

B.S., Computer Science with Mathematics minor, University at Buffalo, 1990

Research Interests

My research interests are in applying computational science algorithms to the determination of the three-dimensional structures of macromolecular complexes using a variety of biophysical techniques. The current focus of my research is aimed at developing icosahedral virus software that will allow easy, efficient, and routine determination icosahedral viruses structures. My research employs algorithms from artificial intelligence, image processing, pattern recognition, optimization, and three-dimensional visualization.

Experience

Director of Research and Founder, 1998 - present

QED Labs, San Jose, CA.

  • Icosahedral virus structure determination software. Research funded by the National Institute of General Medical Sciences, National Institutes of Health Small Business Innovative Research Grant (R44 GM58327)

Research Associate, 1997 - 1999

Department of Biochemistry, Baylor College of Medicine.

  • Direct visualiation and difference imaging based localization of an altered arrangement of scaffolding within the bacteriophage P22 procapsid through three-dimensional electron microscopy structure determination. Based on these observations proposed a model for why the mutant prevents scaffolding release and capsid maturation.
  • Proposed models for how the binding interactions of scaffolding and DNA with the coat shell of bacteriophage P22 may act to control the packaging of the DNA into the expanding procapsids based on three-dimensional structures of the bacteriophage P22 procapsid and mature phage.
  • Developed a method for determination of the image degradation functions present in electron cryomicroscopy images using a hybrid solution x-ray scattering and electron microscopy image processing approach. Usage of this method allows more accurate three-dimensional structure determination.
  • Identified the location of the coat/scaffolding protein interface in the bacteriophage P22 procapsid through three-dimensional structure determination and difference imaging. Developed a model for scaffolding-directed virus assembly based upon this identified location of coat/scaffolding interaction.
  • Lead research projects of two post-doctoral fellows at the National Center for Macromolecular imaging. Projects involved improvements to automated particle selection using wavelets and fuzzy C-means clustering, and three-dimensional structural studies of the bacteriophage P22 infectious phage.

W. M. Keck Center for Computational Biology Post-doctoral Fellow 1996 - 1997

Department of Computational and Applied Mathematics, Rice University.

  • Developed and implemented enhanced computational algorithms for determination of the icosahedral virus particle image orientations needed for three-dimensional reconstruction. The improved methods determine the orientations of more particle images with better accuracy than previous methods. The resulting software is publicly available for use by the electron microscopy community.
  • Determined the three-dimensional structures of bacteriophage P22 procapsids assembled in the absence of the scaffolding protein. These structures show that procapsids assembled in the absence of the scaffolding protein form both T = 4 and T = 7 icosahedral lattices and suggest a role for the scaffolding protein in procapsid size determination.

National Library of Medicine Pre-doctoral Fellow 1993 - 1996

Program in Structural and Computational Biology, Baylor College of Medicine.
Ph. D. Thesis: Computational improvements in the determination of icosahedral virus structures using electron cryo-microscopy and structural studies of scaffolding-containing procapsids.

  • Developed and implemented a method to automatically detect the locations of virus particle images from noisy low contrast electron microscopy images. The resulting software is publicly available for use by the electron microscopy community.
  • Determined the 19 Å resolution structure of the scaffolding-containing bacteriophage P22 procapsid. This structure revealed previously unknown structural characteristics of the P22 coat protein gp5. In addition, this structural study showed that the scaffolding protein is not packed icosahedrally within the procapsid.

Research Assistant under Nobel Laureate Herb Hauptman 1989 - 1992

Department of Computer Science, State University of New York at Buffalo and the Hauptman-Woodward Research Institute.
M. S. Thesis: Solutions to the phase problem of x-ray crystallography on a variety of parallel machines.

  • Primary developer of novel algorithms for a computational solution to the small molecule phase problem of x-ray crystallography. Research involved integration of parallel computing, minimization techniques, and x-ray crystallography resulting in the Shake-and-Bake method for small molecule structure determination distributed by the Hauptman-Woodward Research Institute.

Teaching Assistant 1991 - 1992

Department of Computer Science, State University of New York at Buffalo.

  • Prepared and taught weekly recitations in advanced data structures and discrete mathematics. Additional duties included preparing and teaching short courses on Ada and programming the Intel ipsc/2 hypercube.

Graduate Assistant 1990 - 1991

Graduate Group in Advanced Scientific Computing, State University of New York at Buffalo.

  • Provided consulting on usage of the iPSC/2 hypercube and other parallel computing issues.

Professional Activities

  • January 2005 - present: Member Biomedical Computing and Health Informatics Study Section, Center for Scientific Review, National Institutes of Health.

Academic Committees

  • Member of the executive committee for the Biomedical Computation and Visualization Laboratory, Baylor College of Medicine, 1995 - 1996.
  • Member of the executive council for the graduate Program in Structural and Computational Biology, Baylor College of Medicine, 1994 - 1995.
  • Program in Structural and Computational Biology representative for the Graduate Student council, Baylor College of Medicine, 1993 - 1995.
  • Vice president of the Computer Science Graduate Student Association, University at Buffalo, 1991 - 1992.

Publications

Peer Reviewed

  1. C. Teschke, A. McGough, and P. Thuman-Commike (2003). Penton Release from P22 Heat-Expanded Capsids Suggests Importance of Stabilizing Penton-Hexon Interactions during Capsid Maturation. Biophysical J., 84:2585-92.
  2. P. Thuman-Commike (2001). Single Particle Macromolecular Structure Determination via Electron Microscopy. FEBS Letters, 505:199-205..
  3. P. Thuman-Commike and W. Chiu. (2000). Reconstruction Principles of Icosahedral virus Structure Determination Using Electron Cryomicroscopy. Micron, 31:687-711.
  4. Z. Zhang, B. Greene, P. Thuman-Commike, J. Jakana, P. Prevelige Jr., J. King, W. Chiu (2000). Visualization of the Maturation Transition in Bacteriophage P22 by Electron Cryomicroscopy. Journal of Molecular Biology, 297: 615-626.
  5. P. Thuman-Commike, B. Greene, J. Jakana, A. McGough, P. Prevelige Jr., W. Chiu (2000). Identification of Additional Coat-Scaffolding Interactions in a Bacteriophage P22 Mutant Defective in Maturation. Journal of Virology. 74:3871-3873.
  6. P. Thuman-Commike, B. Greene, J. A. Malinski, M. Burbea, A. McGough, W. Chiu, P. E. Prevelige Jr. (1999). Mechanism of Scaffolding-Directed Virus Assembly Suggested by Comparison of Scaffolding-Containing and Scaffolding-Lacking P22 Procapsids. Biophysical Journal, 76: 3267-3277.
  7. P. Thuman-Commike, H. Tsuruta, B. Greene, P. E. Prevelige Jr., J. King, and W. Chiu. (1999). Solution X-Ray Scattering Based Estimation of Electron Cryomicroscopy Imaging Parameters for Three-Dimensional Reconstruction. Biophysical Journal, 76, 2249-2261.
  8. P. Thuman-Commike, B. Greene, J. Malinski, J. King, and W. Chiu. (1998). Role of the Scaffolding Protein in P22 Procapsid Size Determination Suggested by T = 4 and T = 7 Procapsid Structures . Biophysical Journal, 74, 559 - 568.
  9. A. M. Paredes, H. Heidner, P. Thuman-Commike, B. V. V. Prasad, R. E. Johnston, and W. Chiu. (1998). Structural Localization of the E3 Glycoprotein in Attenuated Sindbis Virus Mutants. Journal of Virology, 72, 1534 - 1541.
  10. P. Thuman-Commike and W. Chiu. (1997). Improved Common Line-Based Icosahedral Particle Image Orientation Estimation Algorithm. Ultramicroscopy, 68, 231-255.
  11. P. Thuman-Commike, B. Greene, J. Jakana, B. V. V. Prasad, J. King, P. Prevelige Jr., and W. Chiu. (1996). Three-Dimensional Structure of Scaffolding-containing Phage P22 Procapsids by Electron Cryo-microscopy. Journal of Molecular Biology, 260:85-98.
  12. P. Thuman-Commike and W. Chiu. (1996). PTOOL: A Software Package for the Selection of Particles from Electron Cryomicroscopy Spot-scan Images. Journal of Structural Biology, 116:41 - 47.
  13. P. Thuman-Commike and W. Chiu. (1995). Automatic Detection of Spherical Particles from Spot-Scan Electron Microscopy Images. Journal of the Microscopy Society of America, 1, 191-201.
  14. G. DeTitta, C. Weeks, P. Thuman, R. Miller, and H. Hauptman. (1994). Structure Solution by Minimal-Function Phase Refinement and Fourier Filtering I. Theoretical Basis. Acta Crystalographica, A50, 203-210.
  15. C. Weeks, G. DeTitta, H. Hauptman, P. Thuman, and R. Miller. (1994). Structure Solution by Minimal-Function Phase Refinement and Fourier Filtering II. Implementation and Application. Acta Crystalographica, A50, 210-220.
  16. C. Chang, G. DeTitta, H. Hauptman, R. Miller, P. Thuman and C. Weeks. (1993). Using Parallel Computers to Solve the Phase Problem of X-ray Crystallography. International Journal of Supercomputer Applications, 7, 25-49.

Book Chapters

  1. P. Thuman-Commike and W. Chiu. (1999). Icosahedral Virus Structure Determination by Electron Cryomicroscopy: Image Processing Principles. In Focus on Multidimensional Microscopy (volume II) Eds. P. C. Cheng, P.P. Hwang, J. L. Wu, G. Wang, and H. Kim. World Scientific Publishing Company, Singapore, pgs. 11 -41.

Conference Proceedings & Abstracts

  1. A. Saad, W. Chiu, and P. Thuman-Commike. (1998). Multiresolution Approach to Automatic Detection of Spherical Particles from Electron Microscopy Images. Proceedins of the IEEE 5th International Conference on Image Processing. Chicago, IL, W8-10.
  2. P. Thuman-Commike and W. Chiu. (1997). Three-Dimensional Reconstruction of Noisy Electron Microscopy Virus Particle Images. Proceedings of the IEEE 4th International Conference on Image Processing, volume I, 173 - 176.
  3. P. A. Thuman-Commike, B. Greene, J. Jakana, B. V. V. Prasad, W. Chiu, J. King, P. E. Prevelige Jr. (1996). Three-Sdimensional Structure of Scaffolding-Containing Phage P22 Procapsids by Electron Cryomicroscopy. Biophysical Society 40th Annual Meeting, Biophysical Journal, volume 70, A364.
  4. P. Thuman-Commike and W. Chiu. (1995). Detection of Virus Particles in Noisy Spot-Scan Electron Cryomicroscopy Images. Proceedings of the IEEE 2nd International Conference on Image Processing, volume III, 169 - 171.
  5. W. Chiu, J. Jakana, Z. Hong Zhou and P. Thuman-Commike. (1995). 400keV Electron Cryomicroscopy and Computer Reconstruction of Spherical Viruses. Microscopy Society of Canada, volume XXIII, 16 - 17.
  6. C. Chang, G. DeTitta, H. Hauptman, R. Miller, P. Thuman, and C. Weeks. (1994). Searching Over a Domain Critical Function: Recasting the Phase Problem of X-Ray Crystallography. Proceedings of the Ninth IEEE Conference on Artificial Intelligence for Applications, 183-189.
  7. C. Chang, G. DeTitta, H. Hauptman, R. Jones, R. Miller, P. Thuman, C. Weeks. (1993). Solving the Phase Problem of X-Ray Crystallography on Parallel Machines. Proceedings of the 6th SIAM Conference on Parallel Processing for Scientific Computing, 304-307.
  8. C. Chang, G. DeTitta, H. Hauptman, R. Miller, P. Thuman, and C. Weeks. (1992). Solutions to the Phase Problem of X-Ray Crystallography on the Connection Machine CM- 2. Proceedings of the 4th Symposium on the Frontiers of Massively Parallel Computation, 510 - 512.
  9. P. Thuman. (1991). Parallel Minimization Techniques for the Phase Problem in X-Ray Crystallography. Proceedings to the University at Buffalo Graduate Conference in Computer Science, 107 - 115.
  10. G. DeTitta, H. Hauptman, R. Miller, M. Pagels, T. Sabin, P. Thuman, and C. Weeks. (1991). Parallel Solutions to the Phase Problem of X-Ray Crystallography: An Update, Proceedings of the Sixth Distributed Memory Computing Conference, 587 - 594.
  11. G. DeTitta, P. Thuman, and R. Miller. (1991). Some Observations about Computing with More than One Processor. Abstracts of the American Crystallographic Association, Abstract O1, 51.
  12. G. T. DeTitta, C. M. Weeks, P. Thuman, R. Miller, and H. A. Hauptman. (1991). Structure Solution by Minimal Function Phase Refinement and Fourier Filtering: Theoretical Basis. Abstracts of the American Crystallographic Association, Abstract O2, 51.
  13. C. Weeks, G. DeTitta, P. Thuman, R. Miller, and H. Hauptman. (1991). Structure Solution by Minimal Function Phase Refinement and Fourier Filtering: Implementation and Applications. Abstracts of the American Crystallographic Association, Abstract O3, 51.
  14. N. Bashir, M. Crovella, G. DeTitta, F. Han, H. Hauptman, J. Horvath, H. King, D. Lang, R. Miller, T. Sabin, P. Thuman, and D. Velmurugan. (1990). Parallel Solutions to the Phase Problem of X-Ray Crystallography. Proceedings of the Fifth Distributed Memory Computing Conference, 513-521.

Technical Reports

  • C.S. Chang, G. DeTitta, H. Hauptman, R. Miller, P. Thuman, R. Miller. (1992). Using Parallel Computers to Solve the Phase Problem of X-Ray Crystallography. Technical Report 92-15, Department of Computer Science, University at Buffalo.

    • Invited Presentations

    • Mechanisms of Virus Assembly and Maturation Investigated by Structural Studies of Bacteriophage P22. Department of Molecular and Cell Biology, University of Connecticut, Storrs. Departmental Seminar. July 1999.
    • Structural Studies of Bacteriophage P22 Procapsids Assembled in the Absence of the Scaffolding Protein. Program in Structural and Computational Biology and Molecular Biophysics Faculty Seminar Series. February 1997.
    • Computational Methods for the Determination of Icosahedral Virus Structures Using Electron Cryo-Microscopy. ASBMB Fall Symposium on Computational Biology: Methods in Biomolecular Imaging, October 1996.
    • Three-dimensional Structure of the Bacteriophage P22 Procapsid, invited speaker, Baylor College of Medicine Graduate Student Symposium. March, 1996.
    • Computational Methods for Icosahedral Particle Reconstruction of Bacteriophage P22, invited speaker, Annual National Library of Medicine Medical Informatics Trainees and Directors Meeting. June 1995.
    • Parallel Computation of the Minimal Function, invited speaker, Medical Foundation of Buffalo Symposium on the Phase Problem of X-Ray Crystallography. December 5, 1990.