Troy C. Messina

Assistant Professor of Physics (2007-present)
Broyle's Inaugural Year Research Chair (2007-2008)
Gus S. Wortham Chair of Engineering (2008-present)
University of Texas at Austin, B.S.,1996; M.A., 1999, Ph.D., 2002

Contact Information

Teaching (Spring 2008)

Teaching (Fall 2007)

Research

Professional Experience

  • Assistant Professor of Physics, Centenary College of Louisiana, 2007-present
  • NIH NRSA Ruth L. Kirschstein Post-Doctoral Fellow, Department of Chemistry and Chemical Biology, Rutgers University, 2003-2007
  • Post-Doctoral Research Associate, Department of Physics, Princeton University, 2003
  • Graduate Research Assistant, University of Texas at Austin, Department of Physics, 1995-2002
  • Semiconductor Research Intern, International 300 mm Initiative/International Sematech, Austin, TX, 1997-2000
  • Contract Scientist, Xidex Corporation, Austin, TX, 1999-2000

Personal Interests

Past Research Projects

  • Glucose/Galactose Binding Protein

    Enteric bacteria use glucose/galactose binding protein (GGBP) in separate pathways to actively transport methylgalactosides across the cell membrane and to chemically sense them as part of the swimming regulatory scheme. Crystallographic and bulk steady-state experiments have been reported for GGBP. Binding of glucose has been described both by a single and by multiple binding constants. GGBP undergoes large dynamic structural fluctuations that are decreased, but not eliminated upon binding of glucose. Thermodynamic characterisation of the structural changes associated with ligand recognition and protein-complex docking can be difficult and detailed understanding of the role of conformation in ligand binding and delivery to the cytosol or activation of the methyl accepting chemotaxis protein Trg are not well characterized.

    We show that GGBP fluctuates between at least three conformations with the relative weights of those conformations being modulated by the binding of glucose. Each structure has different binding affinity and thermodynamic properties. The single binding site of GGBP was considered to have a single association constant, our results suggest that the binding constant is conformationally dependent. Moreover, the ligand binding does not induce the conformational change, rather, it biases the distribution of conformation by stabilising the high-affinity receptor-competent structures. Computational predictions for the closely related ribose binding protein show qualitatively similar results.12 The presence of two high-affinity binding structures is suggestive of the different membrane receptors to which GGBP must bind to provide either active transport or chemotaxis. Conformational plasticity is increasingly becoming recognised as an important issue in drug resistance. GGBP is an ABC transporter system which are common targets for therapeutics. An inhibitor for flexible targets like GGBP would need to interact with all parts of the binding-competent conformational ensemble. Glucose/galactose binding protein (GGBP) is a component of the the ?-methyl galactoside chemosensory transport system in Escherichia coli responsible for delivery of glucose and galactose to periplasmic membrane receptor proteins. Previous studies of GGBP have shown large-scale conformational changes upon ligand binding.

    preprint
    supplemental info

  • Hidden Markov Model Analysis of Multichromophore Photobleaching

    The interpretation of single-molecule measurements is greatly complicated by the presence of multiple fluorescent labels. However, many molecular systems of interest consist of multiple interacting components. We address this issue using multiply-labeled dextran polymers that we intentionally photobleach to the background on a single molecule basis. Hidden Markov models allow unsupervised analysis of the data to determine the number of fluorescent subunits involved in the fluorescence intermittency of the 6-carboxy-tetramethylrhodamine labels by counting the discrete steps in fluorescence intensity. The Bayes information criterion allows us to distinguish between hidden Markov models that differ by number of states, i.e., number of fluorescent molecules. We determine information-theoretical limits and show via Monte Carlo simulations that the hidden Markov model analysis approaches these theoretical limits. This technique has resolving power of one fluorescing unit up to as many as 30 fluorescent dyes with the appropriate choice of dye and adequate detection capability. We discuss the general utility of this method for determining aggregation-state distributions as could appear in many biologically important systems and its adaptability to general photometric experiments.

    preprint

  • Reconstructing Langevin Dynamics with Hidden Markov Models

    I am currently using HMM to analyze Langevin dynamics on a double-well potential. These HMM use lifetime and the known potential of mean force to reconstruct the photon trajectory for a protein labeled with two chromophores. The goal is to identify limits of barrier heights, friction coefficients, Forster distance, and potential curvature for trajectory reconstruction.

    (a) Potential of mean force used to describe the protein dynamics dictated by a FRET fluorophore pair (donor and acceptor) distance attached to a protein. The residence probability distribution function is overlaid.

    (b) Simulated photon trajectories recorded by donor (red) and acceptor (blue) channels.

    (c-d) Microtime (the time lag between the laser pulse and the arrival of the photon) for each photon recorded in donor channel (c) and acceptor channel (d).

    (e) Reconstructed donor-acceptor distance trajectory using hidden Markov model (HMM) with evenly spaced 21 states across the donor-acceptor distance.

    (f) “True” donor-acceptor distance trajectory, generated by Langevin dynamics simulation on (a).

  • Molecular Dynamics Simulations of GGBP

    Using IMPACT (an implicit solvent, all-atom molecular dynamics package), I performed umbrella-potential sampling molecular dynamics simulations of GGBP. In the absence of crystallographic data, one can steer the protein conformation and systematically search for and minimize the energy of conformational structures along a sensible pathway. Once the minimized structures are obtained, molecular dynamics simulations will populate the structures, and from the relative populations, one can extract the potential of mean force on a two-dimensional (theta, phi) coordinate system. Shown in the images are contour plots of the holo (glucose-free) and apo (glucose-bound free energy surfaces (PMFs) of GGBP.

Publications

  1. T. C. Messina and D. S. Talaga, "Free energy landscapes remodeled by ligand binding," Biophys. J. 93 579-585 (2007).

  2. T. C. Messina, C. W. Miller, and J. T. Markert, "Observation of steric quenching of the switchable mirror effect in Y1-zSczHx," Phys. Rev. B 75 104109-10411 (2007).

  3. T. C. Messina, H. Kim, J. T. Giurleo, D. S. Talaga, "Hidden Markov Model Analysis of Multichromophore Photobleaching," J. Phys. Chem. B 110, 16366-16376 (2006).

  4. J.-H. Choi, T. C. Messina, J. Yan, G. I. Drandova, and J. T. Markert, "Thermal Conductivity and 89Y NMR of Ca2+xY2-xCu5O10," J. of Magn. Mag. Mat. 272, 970-971 (2004).

  5. T. C. Messina, L. N. Dunkleberger, G. A. Mensing, A. S. Kalmbach, R. Weiss, D. Beebe, L. L. Sohn, "A Novel Sensor for Biological Discrimination," The 7th International Conference on Miniaturized Chemical and BioChemical Analysis Systems, Squaw Valley, CA, USA, 5-9 October 2003.

  6. C.W. Miller, U. Mirsaidov, T.C. Messina, J.T. Markert,"External Field Effects on Characteristics of Magnetically-Capped Oscillators for Magnetic Resonance Force Microscopy," J App. Phy.
    93, 6572 (2003).

  7. T. C. Messina, C. W. Miller, J. T. Markert, "Steric Effects in the Metal-Insulator (Mirror-Transparent) Transition in YHx," J. Alloys and Compounds 356-357 181 (2003).

  8. J.T. Markert, T.C. Messina, B. Dam, J. Huijbregste, J.H. Rector, and R. Griessen, "Infinite-Layer Copper-Oxide Laser-Ablated Thin Films: Substrate, Buffer-Layer, and Processing Effects," IEEE Transactions on Applied Superconductivity, 13, 2684 (2003).

  9. G. I. Drandova, T. C. Messina, J. T. Markert, "NMR of 89Y in the Copper-Oxide Spin-Chain Compound Ca2+xY2-xCu5O10," J. Low Temperature Physics 131, 305 (2003).

  10. K. Mochizuki, J.-H. Choi, T. C. Messina, Y. Ando, K. Nakamura, J. T. Markert, "Extreme Smallness of the Transverse Force on Moving Vortices," Physica C 388-389, 705 (2003).

  11. J. Barnett, D. Riley, T. Messina, P. Lysaght, "Wet Etch Enhancement of HfO2 Films by Implant Processing," Solid State Phenomena 92, 11 (2003).

  12. P. S. Lysaght, P. J. Chen, R. Bergmann, T. Messina, R. W. Murto and H. R. Huff, "Experimental Observations of the Thermal Stability of High-k Gate Dielectric Materials on Silicon," Journal of Non-Crystalline Solids, 303, 54 (2002).

  13. M. D. Chabot, T.C. Messina, V. Manicevski, C. W. Miller, J. T. Markert, "Single-Crystal Silicon Triple-Torsional Micro-Oscillators for Use in Magnetic Resonance Force Microscopy", SPIE-Int. Soc. Opt. Eng. Proceedings of Spie - the International Society for Optical Engineering 4559, 24 (2001).

  14. J. T. Markert, T. C. Messina, B. Dam, J. Huijbregste, J. Rector, R. Griessen, "Observation of Step-Flow Growth in Laser-Ablated thin films of the T'-Phase compound Pr2CuO4," Physica C, 341-348, 2355-56 (2000).

  15. J. T. Markert, T. C. Messina, B. Dam, J. Huijbregste, J. H. Rector, R. Griessen, "Laser-Ablated Thin Films of Infinite-Layer Compounds and Related Materials," Proceedings of SPIE 4058, 141 (2000).

  16. T. Ono, G. A. Rozgonyi, C. Au, T. C. Messina, R. Goodall, H. R. Huff, "Oxygen Precipitation Behavior in 300mm Polished Czochralski Silicon Wafers," J.Electrochem. Soc. 146, 3807
    (1999).

  17. H. R. Huff, D. McCormack Jr., C. Au, T. C. Messina, K. Chan, R. Goodall, "Current Status of 200mm and 300mm Silicon Wafers," Proceedings of the Intl. Solid StateDevices and Materials (ISSDM '97), Japan, p. 456 and Conference Abstracts p.575, (1997) also published in Jpn J. Appl Phys, 37, (1998) Pt.1, No.3B.

  18. C. Au, T. C. Messina, R. Goodall, H. R. Huff, "Characterization of 300mm Polished Silicon Wafers," Proceedings of the 8th International Symposium on Silicon Materials and Technology, 1, p.641, (1998).

  19. T. C. Messina, C. Au, S. Shih, Z. Yang, R. Goodall, H. R. Huff, "Current Status of 300mm Wafer Characterization," Proceedings of the International Mechanical Engineering Conference and Exposition (IMECE '98), p.825, (1998).

  20. S. Shih, C. Au, Z. Yang, T. C. Messina, R. Goodall, H. R. Huff, "Characterization of 300mm Silicon-Polished and Epi Wafers," Microelectronic Engineering 45, 169 (1999).

  21. J. T. Markert, K. Mochizuki, T. C. Messina, B. C. Dunn, A. V. Elliott,"Studies of Infinite-Layer, T'-Phase, and 1-D Ladder Copper-Oxide Compounds," Physics and Materials Science of High Temperature Superconductor, IV. Proceedings of the NATO Advanced Research Workshop. Kluwer Academic Publishers. 1997, pp.151.