Links for Additional Information

Mark Bathe, Ph.D.

Department of Biological Engineering
Associate Professor

Building 16, Room 255
617-324-5685 (phone)

Biosketch

B.Sc. Mechanical Engineering, MIT, 1998
M.Sc. Mechanical Engineering, MIT, 2001
Ph.D. Mechanical Engineering, MIT, 2004
Postdoctoral Fellow, University of Munich, 2005-2008
Assistant Professor, 2009-2013
Associate Professor, 2014-present

Research Summary

Structural DNA Nanotechnology

Synthetic nucleic acid assemblies can now be programmed to self-assemble with high structural fidelity using Watson-Crick base-pairing. This synthetic structural approach offers unprecedented control over the 3D architecture and chemical composition of large-scale macromolecular assemblies that can also be interfaced with natural and synthetic molecules inside and outside of the cell. Here, we are developing computational strategies to enable high-throughput and high fidelity design and synthesis of arbitrary geometries, sizes, and sequences of DNA-based nanostructures for diverse applications in nanobiotechnology. In related work we are exploring use of these scaffolds for organizing toxins, viral coat proteins, chromophores, enzymes, lipids, and RNAs in complex 3D architectures for applications ranging from cellular drug targeting and delivery to biosensing and chemical synthesis. This work is funded by the ONR, NSF, and HFSP.

Programmed Nanoscale Energy Transport

Natural photosynthetic complexes consist of highly structured geometric assemblies of chlorophyll molecules that facilitate photon adsorption and energy transfer for the production of chemical fuel. Programmed self-assembly of DNA into precise 3D architectures can now be used to organize synthetic chromophores to replicate key aspects of bacterial photosynthetic systems. In this work, we are using structure-based design algorithms to program novel energy harvesting and transfer complexes using scaffolded DNA origami. We additionally synthesize these DNA-chromophore assemblies to test their programmed function to feedback to their rational structure-based design. This work is funded by the ARO and is in collaboration with the Yan Lab and the Aspuru-Guzik Lab.

Multiplexed Imaging of Neuronal Synapse Proteins

Neuronal synapses consist of thousands of proteins organized on the sub-micron scale, mediating neuronal signal transmission and circuit function in the brain. While genetic aberrations in neuronal synapse proteins including receptors and scaffolding molecules are known to be associated with a number of neurological and psychiatric diseases, it is unclear how these genetic aberrations affect synapse function through protein expression level, localization, and organization. In this research we are applying PAINT (Points Accumulation for Imaging in Nanoscale Topography) imaging that enables highly multiplexed super-resolution imaging of synaptic proteins by sequentially applying transiently binding imaging probes that recognize distinct antibodies targeting synaptic proteins. This approach enables the simultaneous in situ super-resolution imaging of arbitrary numbers of molecular targets in normal and diseased brain tissue to resolve the impact of genetic mutations on changes in synaptic protein copy number and co-localization. This work is funded by the NIH and is in collaboration with the Boyden Lab and the Yin Lab.

Bacterial Cell Wall Growth and Growth Inhibition

The cell shape and structural rigidity of Bacillus subtilis, a rod-like bacteria, is conferred through its peptidoglycan (PG)-based cell wall, and characterization of the machinery that governs PG synthesis, crosslinking, and eventual cell elongation remains incomplete. Elucidation of the interactions between these peptidoglycan-synthesizing proteins (PGSP) has the potential to reveal new targets for antibiotics and further our understanding of mechanisms of drug resistance in this and other bacterial species. In this work we are studying the PGSP interactome through quantitative time-lapse imaging of fluorescent PGSP fusion proteins. We are applying Bayesian inference procedures for single-particle trajectory and fluorescence fluctuation datasets to infer in vivo interdependencies between synthesizing proteins that are essential to B. subtilis growth and shape maintenance. High-throughput and objective statistical analysis of PGSP motion and molecular interactions will set the groundwork for models of bacterial cell wall formation that will lead to new understanding of the biochemistry and mechanics of peptidoglycans, as well as to potential discovery of previously unknown bacterial susceptibilities to pharmacological cell wall disruption. This work is funded by the NSF and is in collaboration with the Garner Lab.

Signaling Localization and Cell Shape Analysis in Migration

Cell migration is a critical process in development, wound healing, and immune response, and its pathophysiological dysregulation is a fundamental hallmark of cancer metastasis. A systems-level characterization of how cells process external cues to initiate local activation of signaling cascades that lead to particular cell shapes and motility responses will enhance our understanding of mechanisms that govern cell migration. In this work we are applying live-cell imaging and cell shape analysis to characterize dynamical aspects of cell migration that integrate measurements of spatial and temporal features of signaling pathway activities, cell shape, and migratory response under the influence of physiologically-relevant extracellular perturbations. Models of this process seek to fill two fundamental gaps within the cell migration research field: the low-throughput nature of live cell imaging used to quantify cell motility, and the limited understanding of how molecular components of signaling pathways collectively orchestrate spatiotemporal polarization in cell shape during early stages of migration. This work is funded by the NSF and is in collaboration with the Lauffenburger Lab.

Publications

[47] Wang, P., Gaitanaros, S., Lee, S., Bathe, M., Shih, W.M., Ke, Y. Programming Self-Assembly of DNA Origami Honeycomb Lattices and Plasmonic Metamaterials. Submitted (2015).

[46] Su, K.C., Barry, Z., Schweizer, N., Maiato, H., Bathe, M., Cheeseman, I. A regulatory switch alters chromosome motions at the metaphase to anaphase transition. Submitted (2015).

[45] Boulais, E., Sawaya, N., Veneziano, R., Andreoni, A., Lin, S., Woodbury, N., Yan, H., Aspuru-Guzik, A., Bathe, M. Programmed coherent coupling in a DNA-based excitonic circuit. Submitted (2015).

[44] Katz, Z.B., English, B.P., Lionnet, T., Yoon, Y.J., Monnier, N., Ovryn, B., Bathe, M., Singer, R.H. Mapping translation in live cells by tracking single molecules of mRNA and ribosomes. eLife, in press (2015).

[43] Dhakal, S., Adendorff, M., Liu, M., Yan, H., Bathe, M., Walter, N. Rational design of DNA-actuated enzyme nanoreactors guided by single molecule analysis. Nanoscale, DOI: 10.1039/C5NR07263H (2015). [ Article ]

[42] Hogstrom, L., Guo, S.M., Murugadoss, K., Bathe, M. Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length-scales. Journal of The Royal Society Interface, DOI: 10.1098/rsfs.2015.0081 (2015). [ Article ]

[41] Gordonov, S., Hwang, M.K., Wells, A., Gertler, F.B., Lauffenburger, D., Bathe, M. Time-series modeling of live-cell shape dynamics for image-based phenotypic profiling. Integrative Biology, DOI: 10.1039/C5IB00283D (2015). [ PubMed Article ]

[40] Sedeh, R.Pan, K.Adendorff, M., Hallatschek, O., Bathe, K.J., Bathe, M. Computing nonequilibrium conformational dynamics of structured nucleic acid assemblies. Journal of Chemical Theory & Computation, DOI: 10.1021/acs.jctc.5b00965 (2015). [ PubMed Article ]

[39] Monnier, N.Barry, Z., Park, H.Y., Su, K.C., Katz, Z., English, B., Dey, A.Pan, K., Cheeseman, I., Singer, R., Bathe, M. Inferring transient particle transport dynamics in live cells. Nature Methods, 12: 838 (2015). [ PubMed Article ]

[38] Sun, G., Guo, S.M., Teh, C., Korzh, V., Bathe, M., Wohland, T. Bayesian model selection applied to the analysis of FCS data of fluorescent proteins in vitro and in vivo. Analytical Chemistry, 87: 4326 (2015). [ PubMed Article ]

[37] Zhou, Z., Munteanu, E.L., He, J., Ursell, T., Bathe, M., Huang, K.C., Chang, F. The contractile ring coordinates curvature dependent septum assembly during fission yeast cytokinesis. Molecular Biology of the Cell, 26: 78 (2015). [ PubMed Article ]

[36] Pan, K.Kim, D.N., Zhang, F., Adendorff, M., Yan, H., Bathe, M. Lattice-free prediction of three-dimensional structure of programmed DNA assemblies.Nature Communications, 5: 5578 (2014). [ PubMed Article ]

[35] Klingner, C., Cherian, A.V., Diesinger, P.M., Aufschnaiter, R., Maghelli, N., Keil, T., Beck, G., Tolic-Norrelykke, I., Bathe, M., and Wedlich-Soldner, R. An isotropic acto-myosin network promotes organization of the apical cell cortex in epithelial cells. The Journal of Cell Biology, 207: 107-121 (2014). [ PubMedArticle ]

[34] Sun, W., Boulais, E.Hakobyan, Y., Wang, W., Guan, A., Bathe, M., Yin, P. Casting inorganic structures with DNA molds. Science 346: 717 (2014). [PubMed Article ]

[33] Mori, M., Somogyi, K., Kondo, H., Monnier, N., Falk, H., Machado, P., Bathe, M., Nedelec, F., and Lenart, P. An Arp2/3 nucleated F-actin shell fragments nuclear membranes at nuclear envelope breakdown. Current Biology, 24: 1421-1428 (2014). [ PubMed Article ]

[32] Oh, H.S., Bryant, K.F., Nieland, T., Mazumder, A., Bagul, M., Bathe, M., Root, D.E. and Knipe, D.M. Targeted RNAi Screen Reveals Novel Epigenetic Factors that Regulate Herpesviral Gene Expression in U2OS Osteosarcoma Cells. mBio, 5: e01086-13 (2014). [ PubMed Article ]

[31] Guo, S.M., Bag, N., Mishra, A., Wohland, T., Bathe, M. Bayesian total internal reflection fluorescence correlation spectroscopy reveals hIAPP-induced plasma membrane domain organization in live cells. Biophysical Journal, 106: 190-200 (2014). [ PubMed Article ]

[30] Pan, K., Boulais, E., Yang, L., Bathe, M. Structure-based model for light-harvesting properties of nucleic acid nanostructures. Nucleic Acids Research, 42: 2159-2170 (2014). [ PubMed Article ]

[29] Subramanian, V., Mazumder, A., Surface, L.E., Butty, V., Fields, P.A., Alwan, A., Torrey, L., Thai, K.K., Levine, S., Bathe, M., Boyer, L. H2A.Z acidic patch couples chromatin dynamics to regulation of developmental gene expression programs during lineage commitment. PLoS Genetics, 9: e1003725 (2013). [PubMed Article ]

[28] Mazumder, A., Pesudo, L.Q., McRee, S., Bathe, M., Samson, L. Genome-wide single-cell-level screen for protein abundance and localization changes in response to DNA damage in S. cerevisiae. Nucleic Acids Research, 41: 9310-9324 (2013). [ PubMed Article ]

[27] Johnson-Buck, A., Nangreave, J., Kim, D.N.Bathe, M., Yan, H., Walter, N. Super-resolution fingerprinting detects chemical reactions and idiosyncrasies of single DNA pegboards. Nano Letters, 13: 728-733 (2013). [ PubMed Article ]

[26] Mazumder, A.Tummler, K.Bathe, M., Samson, L.D. Single-cell analysis of RNR transcriptional and translational response to DNA damage. Molecular & Cellular Biology, 33: 635-642 (2013). [ PubMed Article ]

[25] Krishnan, Y., Bathe, M. Designer nucleic acids to probe and program the cell. Trends in Cell Biology, 22: 624-633 (2012). [ PubMed Article ]

[24] Schmidt, J.C., Arthanari, H., Boeszoermenyi, A., Dashkevich, N.M., Wilson-Kubalek, E., Monnier, N., Markus, M., Oberer, M., Milligan, R., Bathe, M., Wagner, G., Grishchuk, E.L., Cheeseman, I.M. The kinetochore-bound Ska1 complex tracks depolymerizing microtubules by binding to curved protofilaments.Developmental Cell, 23: 968-980 (2012). [ PubMed Article ]

[23] Monnier, N.Guo, S.M., Mori, M., He, J., Lenart, P., Bathe, M. Bayesian approach to MSD-based analysis of particle motion in live cells. Biophysical Journal, 103: 616-626 (2012). [ PubMed Article ]

[22] Guo, S.M.He, J.Monnier, N., Sun, G., Wohland, T., Bathe, M. Bayesian approach to the analysis of fluorescence correlation spectroscopy data II: Application to simulated and in vitro data.Analytical Chemistry, 84: 3880-3888 (2012). [ PubMed Article ]

[21] He, J.Guo, S.M.Bathe, M. Bayesian approach to the analysis of fluorescence correlation spectroscopy data I: Theory. Analytical Chemistry, 84: 3871-3879 (2012). [ PubMed Article ]

[20] Kim, D.N., Kilchherr, F., Dietz, H., Bathe, M. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures. Nucleic Acids Research, 40: 2862-2868 (2012). [ PubMed Article ]

[19] Castro, C.E., Kilchherr, F., Kim, D.N., Lin Shiao, E., Wauer, T., Wortmann, P., Bathe, M., Dietz, H. A primer to scaffolded DNA origami. Nature Methods, 8: 221-229 (2011). [ PubMed Article ]

[18] Mori, M., Monnier, N., Daigle, N., Bathe, M., Ellenberg, J., Lenart, P. Intracellular transport by an anchored homogeneously contracting F-actin meshwork. Current Biology, 21: 606-611 (2011). [PubMed Article ]

[17] Kim, D.N., Altschuler, J., Strong, C., McGill, G., Bathe, M. Conformational dynamics data bank: a database for conformational dynamics of proteins and supramolecular protein assemblies. Nucleic Acids Research, 39: D451-455 (2011). [ PubMed Article ]

[16] Kim, D.N.Nguyen, C.T.Bathe, M. Conformational dynamics of supramolecular protein assemblies. Journal of Structural Biology, 173: 261-270 (2011). [ PubMed Article ]

[15] Strehle, D., Schnauss, J., Heussinger, C., Alvarado, J., Bathe, M., Kaes, J., Gentry, B. Transiently crosslinked F-actin bundles. European Biophysical Journal, 40: 93-101 (2011). [ PubMed Article ]

[14] Sedeh, R.S., Fedorov, A.A., Fedorov, E.V., Ono, S., Matsumura, F., Almo, S.C., Bathe, M.Structure, evolutionary conservation, and conformational dynamics of Homo sapiens fascin-1, an F-actin crosslinking protein. Journal of Molecular Biology, 400: 589-604 (2010). [ PubMed Article ]

[13] Bathe, M., Chang, F.C. Cytokinesis and the contractile ring in fission yeast: towards a systems-level understanding. Trends in Microbiology, 18: 38-45 (2010). [ PubMed Article ]

[12] Sedeh, R.Bathe, M., Bathe, K.J. The subspace iteration method in protein normal mode analysis. Journal of Computational Chemistry, 31: 66-74 (2010). [ PubMed Article ]

Pre-2009

[11] Bathe, M., Heussinger, C., Claessens, M.M.A.E., Bausch, A.R., and Frey, E. Cytoskeletal bundle mechanics. Biophysical Journal, 94: 2955-2964 (2008). [PubMed Article ]

[10] Bathe, M. A Finite Element framework for computation of protein normal modes and mechanical response. Proteins: Structure, Function, and Bioinformatics, 70: 1595-1609 (2008). [PubMed Article ]

[9] Heussinger, C., Bathe, M., and Frey, E. Statistical mechanics of wormlike bundles. Physical Review Letters: 99: Art. No. 048101 (2007). [ PubMed Article ]

[8] Claessens, M.M.A.E., Bathe, M., Frey, E., and Bausch, A.R. Actin-binding proteins sensitively mediate F-actin bundle stiffness. Nature Materials, 5: 748-753 (2006). [ PubMed Article ]

[7] Bathe, M., Rutledge, G.C., Grodzinsky, A.J., and Tidor, B. Osmotic pressure of aqueous chondroitin sulfate solution: A molecular modeling investigation.Biophysical Journal, 89: 2357-2371 (2005). [ PubMed Article ]

[6] Bathe, M., Rutledge, G.C., Grodzinsky, A.J., and Tidor, B. A coarse-grained molecular model for glycosaminoglycans: Application to chondroitin, chondroitin sulfate, and hyaluronic acid. Biophysical Journal, 88: 3870-3887 (2005). [ PubMed Article ]

[5] Bathe, M., Grodzinsky, A.J., Tidor, B., and Rutledge, G.C. Optimal linearized Poisson-Boltzmann theory applied to the simulation of flexible polyelectrolytes in solution. Journal of Chemical Physics, 121: 7557-7561 (2004). [ PubMed Article ]

[4] Kaazempur-Mofrad, M.R., Bathe, M., Karcher, H., Younis, H.F., Seong, H.C., Shim, E.B., Chan, R.C., Hinton, D.P., Isasi, A.G., Upadhyaya, A., Powers, M.J., Griffith, L.G., and Kamm, R.D. Role of simulation in understanding biological systems. Computers & Structures, 81: 715-726 (2003). [ PubMed Article ]

[3] Bathe, M. and Rutledge, G.C. Inverse Monte Carlo procedure for conformation determination of macromolecules. Journal of Computational Chemistry, 24: 876-890 (2003). [ PubMed Article ]

[2] Bathe, M., Shirai, A., Doerschuk, C.M., and Kamm, R.D. Neutrophil transit times through pulmonary capillaries: The effects of capillary geometry and fMLP-stimulation. Biophysical Journal, 83: 1917-1933 (2002). [ PubMed Article ]

[1] Bathe, M. and Kamm, R.D. A fluid-structure interaction finite element analysis of pulsatile blood flow through a compliant stenotic artery. Journal of Biomechanical Engineering, 121: 361-369 (1999). [ PubMed Article ]

Last Updated: January 13, 2016