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Scholarly Interest Report
         
Michael Diehl
Associate Professor
Associate Professor of Bioengineering and Chemistry
 
e-mail:diehl@rice.edu
 
  • B.S. Chemistry (1997) The College of New Jersey, New Jersey
  • Ph.D. Chemistry (2002) University of California, Los Angeles
  • Beckman Senior Research Fellow (2002-2005) California Institute of Technology
 
Primary Department
   Department of Bioengineering
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Department Affiliations
 
  • Department of Chemistry
  •  
    Websites
     Diehl Lab
     Michael R. Diehl
     
    Research Areas
     Intracellular Transport, Biomolecular Imaging, Supramolecular Biophysics, Biomaterials, Protein and Molecular Bioengineering
     
    Michael Diehl Research Statement 2005
     Our laboratory strives to understand the cooperative dynamics of proteins when they operate as highly organized and integrated assemblies. We adopt engineering approaches that enable model systems of natural multiprotein assemblies to be reconstructed in vitro while preserving the intricate molecular features of these assemblies. Our techniques allow the molecular orchestration of interacting proteins to be sensitively probed, while defining specific molecular interactions that are normally confounded by the diversity of cellular environments. In this way, we are able to bridge the gaps between our understanding of the stochastic dynamics of isolated single molecules and the operation of multiprotein assemblies in physiological settings. This research naturally involves a combination of state-of-the-art synthetic techniques to construct multiprotein architectures, and the development of instrumentation to investigate collective protein dynamics with single-molecule precision. While our methods can be generalized, enabling investigation of a variety of multiprotein networks and assemblies, so far this research concentrates on two areas:



    IN VITRO MODELING OF INTRACELLULAR TRAFFICKING AND TRANSPORT:

    The transport of intracellular cargo to different locations of the cell involves the activated mechanics of biomotor proteins. In many cases, these proteins interact with one another, as well as their associated regulatory proteins, in order to control and optimize transport. We seek to understand mechanistic pictures of these processes by reconstructing these assemblies in vitro and investigating their cooperative dynamics using single-molecule microscopy and spectroscopy techniques. Assemblies are constructed using engineered molecular scaffolds, the properties of which are defined by artificial proteins and DNA nanostructures. These scaffolds provide a means to accurately specify the supramolecular architecture of assemblies by defining the number and types of coupled motors, intermotor distances, and the elasticity of motor interconnects. These capabilities will enable us to develop detailed structure-activity relationships that will unveil the fundamental scaling laws that govern collective biomotor transport. Furthermore, we can probe the molecular orchestration that occurs within these assemblies with single-molecule sensitivity, bringing new insight to our understanding of the rich dynamics observed during motor driven intracellular transport.



    ENCODING THE SELF-ORGANIZED MECHANICS OF INTERNALLY DRIVEN FILAMENTS:

    The ability to generate coherent and sustained oscillations in highly viscous and damped cellular environments is of fundamental importance in biology. This type of mechanics provides cells with a means for self-propulsion and to stir their surrounding fluids using the controlled beating of internally driven filaments. Similar mechanical behavior is harnessed by cells to detect and amplify extremely small signals, which in some cases, are no larger than thermal noise. Motions of these filaments are self-generated by large collections of biomotor proteins that are arranged into complex architectures, such as those seen in axonemal cilia and flagella. With these systems as inspiration, we are engineering model biomotor assemblies that operate as shearing-mode oscillators, and emulate the dynamics of axonemal assemblies. Using artificial proteins to define and tune the properties of biomotors and nanomechanical devices to probe the motions of these motors, we are developing strategies to encode the cooperative dynamics of internally driven filaments. These efforts will impact our fundamental knowledge of collective biomotor mechanics, and provide guidelines to harness the mechanochemical mechanisms cells employ to sense, respond, and adapt to their surroundings.
     
    Selected Publications
     Refereed articles
     

    A.K. Efremov, A. Radhakrishan, D. Tsao, C.S. Bookwalter, K.M. Trybus, M.R. Diehl “Delineating cooperative responses of processive motors in living cells” accepted to PNAS (2013)

     
     

    D.K. Jamison, J.D. Driver, M.R. Diehl “Structure-function analyses of single, multiple motor complexes” invited and in preparation for special issue in Methods in Enzymology (October 2013).

     
     

    D.S. Tsao, M.R. Diehl. “Molecular motors: myosins move ahead of the pack” Nature Nanotechnology 9, 9-10 (2014).

     
     

    K. Uppulary, J.W. Driver, M.R. Diehl, A.B. Kolomeisky “Analysis of cooperative responses of multiple kinesin motors to structural and chemical factors” Journal of Cellular and Molecular Bioengineering 6, 38-47 (2013). 

     
     A. R. Rogers, J. Driver, P.E. Constantinou, M.R. Diehl Collective transport of interacting kinesin-1 in the absence of applied loads, invited publication to appear in June issue of Physical Chemistry Chemical Physics.
     
     

    D.K. Jamison, A. Rogers, P.E. Constantinou, M.R. Diehl; Enhanced Force Production by Two Interacting Kinesin-1 Motors through the Coupling of Internal Strain Science  Submitted

     
     

    R. Schweller, N. Frankel, P. Constantinou, P. Narayan, M.R. Diehl: Design of DNA-Conjugated Polypeptide-based Capture Probes for the Anchoring of Proteins to DNA Matrices, Bioconjugate Chemistry 19, 2304-2307 (2008).

     
     Articles
     

    D.K Jamison, J. Driver, M.R. Diehl "Cooperative responses of multiple kinesins to variable and constant loads" Journal of Biological Chemistry 287, 3357-3365 (2012)

     
     

    D.Y. Duose, R.M. Schweller, J. Zamak, A. Rogers, W.N. Hittelman, M.R. Diehl "Configuring robust DNA strand displacement reactions for in situ molecular analyses" Nucleic Acids Research 40, 3289-3298 (2012)

     
     

    H. Lu, A.K. Yefremov, C.D. Bookwalter, E.B. Kremestsova, J.W. Driver, K. Trybus, M.R. Diehl "Cooperative dynamics of elastically-coupled myosinV motors" Journal of Biological Chemistry 287, 27253-27761 (2012)

     
     

    J. Zimak, R.S. Schweller, W.N. Hittelman, M.R. Diehl "Programming in situ immunofluorescence intensities through interchangeable reactions of dynamic DNA complexes" ChemBioChem, Dec 21;13(18):2722-8.

     
     

    K. Uppulary, A.K. Efremov, J.W. Driver, D.K. Jamison, M.R. Diehl, A.B. Kolomeisky "How the interplay between mechanical strain and non-mechanical interactions affect multiple kinesin dynamics" Journal of Physical Chemistry B 116, 8846-8855 (2012)

     
     

    K. Uppulary, J.W. Driver, M.R. Diehl, A.B. Kolomeisky “Analysis of cooperative responses of multiple kinesin motors to structural and chemical factors” Journal of Cellular and Molecular Bioengineering: Special issue on biomolecular motors and motor assemblies, 6, 38-47 (2013).

     
     

    M.R. Diehl “Templating a molecular tug-of-war” Science 338, 626-623 (2012)

     
     

    R.S. Schweller, J. Zimak, D.Y. Duose, W.N. Hittelman, M.R. Diehl. "Multiplexed in situ immunofluorescence via dynamic DNA complexes" Angewandte Chemie 51, 9292-9296 (2012)

     
     

    D.Y. Duose, R.M. Schweller, J. Zamak, A. Rogers, W.N. Hittelman, M.R. Diehl “Configuring robust DNA strand displacement reactions for in situ molecular analyses” Nucleic Acids Research, 40, 3289-3298 (2012).

     
     

    D.K Jamison, J. Driver, M.R. Diehl “Cooperative responses of multiple kinesins to variable and constant loads” – Journal of Biological Chemistry 287, 3357-3365 (2012).

     
     

    J.W. Driver, D.K. Jamison, A.R. Rogers, K. Uppulury, A.B. Kolomeisky,  M.R. Diehl “Productive cooperation among processive motors depends on their mechanochemical efficiencies” Biophysical Journal 101, 386 (2011)

     
     

    K.I. McConnell, R.M. Schweller, M.R. Diehl, J. Suh. “Live-cell microarray surface coatings supporting reverse transduction by adeno-associated viruses” BioTechniques 51, 255-258 (2011)

     
     

    D.K. Jamison, J.W. Driver, A.R. Rogers, P.E. Constantinou, M.R. Diehl “Two Kinesins Transport Cargo Primarily via the Action of One: Implications for Intracellular Transport,” Biophysical Journal 99, 2967-2977 (2010).

     
     

    D.W. Driver, A.R. Rogers, D.K. Jamison, R.K. Das., A.B. Kolomeisky, M.R. Diehl “Coupling between Motor Proteins Determines Dynamic Behaviors of Motor Protein Assemblies” Physical Chemistry Chemical Physics 12, 10398 (2010)

     
     

    D.Y. Duose, R.M. Schweller, W.N. Hittelman, M.R. Diehl “Multiplexed and Reiterative Fluorescent Labeling via DNA Circuitry” Bioconjugate Chemistry 21, 2327-2331 (2010).

     
     

    A. R. Rogers, J. Driver, P.E. Constantinou, M.R. Diehl "Negative Interference Dominates Collective Transport of Kinesin Motors in the Absence of Load" PCCP 11, 4882 (2009)

     
     

    P.E. Constantinou, M.R. Diehl "The Macromolecular Hierarchy of Intracellular Transport" Journal of Biomechanics - in press (2009)

     
     

    K. Zhang, M.R. Diehl, D.A. Tirrell "Artificial Polypeptide Scaffold for Protein Immobilization." J. Am. Chem. Soc., 127 (2005) : 10136.

     
     

    M.R. Diehl*, K. Zhang, H.J. Lee, D.A. Tirrell "Engineering Cooperativity in Biomotor-Protein Assemblies." Science, 311 (2006) : 1468.

     
     

    M.R. Diehl, D.W. Steuerman, H-R. Tseng, S.A. Vignon, A. Star, P.C. Celestre, J.F. Stoddart, J.R. Heath "Single-Walled Carbon Nanotube-Based Molecular Switch Tunnel Junctions." Chem. Phys. Chem., 4 (2003) : 1335.

     
     

    M.R. Diehl, J.-Y.Yu, J.R. Heath, G.A. Held, H. Doyle, S. Sun, C.B. Murray "Crystalline, Shape, and Surface Anisotropy in Two Crystal Morphologies of Superparamagnetic Cobalt Nanoparticles by Ferromagnetic Resonance." J. Phys. Chem. B., 105 (2001) : 7913.

     
     

    M.R. Diehl, S. Yaliraki, R. Beckman, M. Barahona, J.R. Heath "Self-Assembled, Deterministic Carbon Nanotube Wiring Networks." Angew. Chem. Int. Ed., 41 (2002) : 353.

     
    Presentations
     Invited Talks
     

    ‘Multi-scale Motility of Molecular Motors’ symposium, Max Plank Institute of Colloids and Interfaces. Potsdam, Germany (September 2013): ‘Synthetic approaches to delineating multiple motor functions in living cells”.

     
     

    Annual CTBS symposium, Innovations in Cellular Systems Biology: Modeling and Imaging session; Houston, TX (November 2012): “In situ proteomic analyses via multiplexed and reiterative imaging approaches”.

     
     

    NSF Center for Computational Physics, Rice University, Houston, Texas (September 2013) “Macromolecular Systems Biology”

     
     

    FASEB ‘Molecular Bioengineering’ symposium; Boston, MA (April 2013): “Single molecule approaches to dissecting network multiple protein functions”.

     
     

    "A. Radhakrishnan (presenter), Artem Efremov, J.C. Meijas, M.R Diehl "Inducible control of kinesin transport in living cells" Horizons in Molecular Biology International Research Symposioum, Goettingen, Germany (2012)." (2012)

     
     

    "Biophysical Society Meeting, Special Session: Cargo transport by multiple motors; San Diego, CA (February 2012): "Collective dynamics of multiple microtubule motors: connecting in vitro observations to in vivo functions"." (February 2012)

     
     

    "Center for Biomolecular Structure and Function, MD Anderson Cancer Center (February 2012): "Macromolecular systems biology"." (February 2012)

     
     

    "Department of Systems Biology, MD Anderson Cancer Center (April 2012): "Macromolecular approaches to systems biology"." (April 2012)

     
     

    "J. Zimak (presenter), R.M. Schweller, D.Y. Duose, M.R. Diehl ‘Discretized antibody signal modulation using branched DNA for fluorescence imaging" Southern Biomedical Engineering Conference, Houston, TX (May 2012)." (May 2012)

     
     

    "J. Zimak (presenter), R.M. Schweller, D.Y. Duose, W.N. Hittelman, M.R. Diehl "Discretized antibody signal modulation using branched DNA for fluorescence imaging" Biomedical Engineering Society Meeting, Atlanta, GA (October 2012)." (October 2012)

     
     

    "M.R. Diehl (presenter) ‘MEMS, NEMS and molecular machines – a tutorial' NANOCOURSE: Design and Implementation for First-in-human oncology trials, MD Anderson Cancer Center (July 2012)." (July 2012)

     
     

    "Multiplexed Imaging conference, MD Anderson Cancer Center (December 2012): "Multiplexed in situ proteomics via dynamic DNA technologies"." (December 2012)

     
     

    "NIH / NCI ‘Innovative Molecular Technologies’ Symposium; Houston TX (November 2012): "Highly-multiplexed, spatially-delineated molecular imaging in cancer"." (November 2012)

     
     

    "R.M. Schweller (presenter), J. Zimak, D.Y. Duose, W.N. Hittelman, M.R. Diehl "High-content molecular imaging and analyses through reactive DNA probe complexes" Southern Biomedical Engineering Conference, Houston, TX (May 2012)." (May 2012)

     
     

    "USACM meeting on Multiscale Methods and Validation in Medicine and Biology: Biomechanics and Mechanobiology; San Francisco, CA (February 2012): "Predicting cooperative dynamics of motor proteins from single-motor measurements"." (February 2012)

     
     

    M.R. Diehl “Macromolecular Systems Bioengineering”.  Department of Bioengineering, University of Washington (January 2011)

     
     

    M.R. Diehl “Principles Governing Cooperation among Processive Molecular Motors” Telluride Science Research Center Workshop: Rise of the Molecular Machines. Telluride, CO (August 2011)

     
     

    M.R. Diehl “Systems and Synthetic Biology Approaches to Investigating Molecular Pathways Governing Intracellular Transport Regulation” Department of Biomedical Engineering, Texas A&M University (March 2011)

     
     

    M.R. Diehl “The Influence of a Processive Motor's Mechanochemical Efficiency on Collective Motor Function” Gordon Research Conference: Muscle and Molecular Motors. Colby Sawyer College, New London, New Hampshire (July 2011)

     
     

    M.R. Diehl “Macromolecular Systems Bioengineering: Structure and Dynamics” Department of Biomedical Engineering, Ohio State University, (April 2010).

     
     

    M.R. Diehl “Synthetic and Biophysical Strategies to Investigate Cooperativity Among Multiple, Interacting, Kinesin-1 Motors” Los Alamos National Labs Conference: Thermodynamics and Kinetics of Molecular Motors, Santa Fe, (May 2010).

     
     

    D.K. Jamison, J.D. Driver, M.R. Diehl “Collective behaviors of multiple interacting kinesin motors: Can kinesin number regulate intracellular transport?” MBI workshop: Transport in the Cell, Columbus, Ohio (April 2010).

     
     

    M.R. Diehl, M.R. “Macromolecular Systems Bioengineering: Structure and Dynamics” Department of Anatomy & Structural Biology, Albert Einstein School of Medicine (January 2010)

     
     

    Diehl, M.R.; Jameson, D.K., Zimmerman, M., Driver, J.D., Rogers, A.R. “Multiple Interacting Kinesin-1 Motors Cooperate Negatively” Biophysical Society Meeting, San Fansico, CA (March 2010).

     
     

    M.R. Diehl “Reiterative Fluorescent Labeling via DNA-Circuitry” NSF: DNA-Nanotechnology Workshop, Oxnard CA (January 2010).

     
     

    M.R. Diehl “The role of multiple motor dynamics in intracellular transport” Department of Molecular Physiology and Biophysics, University of Vermont Medical School (November 2010).

     
     

    M.R. Diehl, Kenneth Jameson, Arthur Rogers. "Collective Stepping Mechanics and Force Production of Two Coupled Kinesin Motors" Motility Subgroup Symposium: National Biophysical Society Meeting Boston, MA (March 2009)

     
     

    M.R. Diehl "Collective Transport of Kinesin-1 Motors" Department of Physics, University of Texas, Austin (September 2009)

     
     

    M.R. Diehl, "Cooperativity in Systems of Two Elastically-Coupled Kinesin Molecules is Force Dependent" Single Molecule Biophysics meeting at the Aspen Center for Physics in Aspen, CO (January 2009)

     
     

    M.R. Diehl "Emergent Properties of Macromolecular Systems Containing Multiple Molecular Motors"   Emergence in Chemical Systems 2.0 conference; Anchorage, AK (June 2009)

     
     

    M.R. Diehl "Macromolecular Systems Bioengineering" Department of Bioengineering, University of California, Berkeley (February 2009)

     
     

    M.R. Diehl "Multiplexed, Reiterative Biomarker Imaging Via DNA Circuit Technologies" Emerging Technologies for Systems Biology Symposium. M.D. Anderson Cancer Center, Houston, TX (August 2009)

     
     

    M.R. Diehl "The Collective Dynamics of Interacting Motor Molecules" Department of Physics, Wake Forest University (November 2009)

     
     Michael R. Diehl A Macromolecular-Systems Approach to Investigating the Collective Dynamics of Interacting Motor Proteins Department of Biochemistry and Cell Biology Rice University August 2008
     
     Michael R. Diehl Arthur Rogers Kenneth Jameson Biosynthetic and Single-Molecule Approaches to Study Multi-motor Transport Recent Advances in Biophysical Chemistry of Transport by Biomolecular Motors and Machines: National ACS Meeting Philadelphia PA August 2008
     
     Biomedical Engineering Society Rita Schafer Planary Lecture, Los Angeles CA. “Engineering Cooperativity in Motor Protein Assemblies”
     
     

    "Investigating multi-protein dynamics with single-molecule sensitivity." Baylor Univ. Department of Chemistry and Biochemistry, Waco TX. (Dec 1, 2006)

     
     Lectures
     

    M.R. Diehl “Molecular Profiling with DNA-Circuitry Probes” NSF: Molecular Programming Workshop, Oxnard CA (June 2011)

     
     Other
     Kenneth Jameson, Arthur Rogers, and Michael R. Diehl Collective Motility and Force-Generation of Exactly Two Coupled Kinesin-1 Motors National American Society of Cell Biology Meeting San Francisco, CA December 2008
     
     Arthur Rogers Kenneth Jamison, Pamela Constantinou, Jonathan Driver, and Michael R. Diehl Single- Molecule Approaches to Investigate Collective Motor Transport Gordon Research Conference: Muscle and Molecular Motors Colby-Sawyer College, New London, NH June 2008
     
     

    "Investigating Integrated Multi-Protein Dynamics with Single-Molecule Sensitivity, Designed Macromolecular Assemblies for Biomedical Applications: National ACS Meeting Chicago, IL (March 2007). ." With Michael R. Diehl, Pamela Constantinou, Dzifa Douse, Arthur Rogers, and Kenneth Jamison

     
     

    "Engineering cooperativity in biomotor-protein assemblies." Gordon Research Conference, New London, NH. (June, 2006)

     
     

    "Self-Assembling Multi-Component Assemblies of Motor Proteins." Biophysical Society, Asilomar, CA. (October 2006) With D. Douse, P Constantinou

     
     Posters
     

    A. Radhakrishnan (presenter), Artem Efremov, J.C. Meijas, M.R Diehl “Synthetic approaches to dissecting intracellular transport mechanisms in living cells” Annual Biophysical Society Meeting, Philadelphia, PA (2013).

     
    Editorial Positions
     Other, Biomech. and Modeling in Mechanobiology. (2013 - 2013)

     Other, Journal of Physics: Condensed Matter. ‘Physics of protein motility / Motor proteins’ (December 2012). (2012 - 2012)

     Other, Advance Functional Materials. (2013 - 2013)

     Other, Advance Functional Materials. (2013 - 2013)

     Other, Physical Biology. (2013 - 2013)

     Other, Nature Nanotechnology. (2013 - 2013)

     Other, ChemPhysChem. (2013 - 2013)

     Other, Neurosurgery. (2013 - 2013)

     Other, Cell Motility and the Cytoskeleton. (2013 - 2013)

     Other, Nature. (2013 - 2013)

     Other, European Journal of Physics. (2013 - 2013)

     Other, PLoS ONE. (2013 - 2013)

     Other, Biomacromolecules. (2013 - 2013)

     Other, Cellular and Molecular Bioengineering. (2013 - 2013)

     Other, Biophysical Journal. (2013 - 2013)

     Other, Advanced Materials. (2013 - 2013)

     Other, MRS Research Journal. (2013 - 2013)

     Other, Nature Reviews. (2013 - 2013)

     Other, PNAS. (2013 - 2013)

     Other, Science. (2013 - 2013)

     Other, Nanoletters. (2013 - 2013)

    Supervised Theses & Dissertations
     Athanasios Dousis, Graduate Student. (Committee Member)

     Konstantin Tsvaygboym. (Committee Member)

     Brian Kirk. (Committee Member)

     Ivan Birukou, BCB. (Committee Member)

     Ting Sun, ECE. (Committee Member)

     Konstantin Tsvaygboym, Bioengineering. (Committee Member)

     Megan Guelker, BCB. (Committee Member)

     Cariss Smith, Chemistry. (Committee Member)

     Brian Kirk, Bioengineering. (Committee Member)

     Athanasios Dousis, Bioengineering. (Committee Member)

    Awards, Prizes, & Fellowships
     NAFKI Keck Futures Award,

     Dissertation Award , Physical Chemistry, University of California at Los Angeles

     HSEMB Outstanding Young Scientist Award,

     IBB Medical Innovation Award,

     Garden State Scholar,

     Beckman Senior Research Fellowship, California Institute of Technology

     Rita Schaffer Young Investigator Award, The Biomedical Engineering Society

     HSEMB Outstanding Young Scientist Award,

     NSF CAREER Award,

     Hamill Research Innovation Award,

     Neshamkin Award in Chemistry,

     Edward J. Bloustein Distinguished Scholar, The College of New Jersey

     W.M. Keck Foundation, Research Excellence Award,

     NIH R21 , NCI (2010-2013)

     Welch Foundation Research Grant, (2006-2012)

     NIH R01 , NIGMS (2010-2015)

     CAREER Award, NSF (2007 - 2012)

     Army Medical Research and Material Command, USARMMC (2009-2011)

     Research Excellence Award, W.M. Keck Foundation (2008)

     Rita Schaffer Young Investigator Award, The Biomedical Engineering Society, (2007)

     Hamill Research Innovation Award, (2006-2007)