CPM Seminar

Probing and programming biomolecular machines using synthetic nucleic acids

Mark Bathe

Department of Biological Engineering
MIT

Synthetic nucleic acids offer a high degree of programmability that enables the custom design of structured biomolecular assemblies at the nanometer-scale, as well as their integration with fluorescence probes to interrogate complex biomolecular machines in living systems. In this talk I will present work in our group to enable the high fidelity design and synthesis of programmed DNA-based assemblies for use in scaffolding chromophores, viral and toxin proteins, and custom RNAs for applications in synthetic biology and membrane biophysics. I will also present development and application of quantitative fluorescence imaging approaches integrated with synthetic RNA and DNA probes to explore mRNA transport and delivery mechanisms in live neurons, as well as quantitation of synaptic protein composition and number using highly multiplexed super-resolution imaging. Together, these examples will illustrate diverse applications of programmed nucleic acids and computation to probe and program biomolecular machines.

References
Monnier, N., Barry, Z., Park, H.Y., Su, K.C., Katz, Z., English, B., Dey, A., Pan, K., Cheeseman, I., Singer, R., Bathe, M. Bayesian classification of single-particle transport dynamics from live-cell imaging data. Submitted (2014).
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, in press (2014).
Sun, W., Boulais, E., Hakobyan, Y., Wang, W., Guan, A., Bathe, M., Yin, P. Casting inorganic structures with DNA molds. Science doi 10.1126/science.1258361 (2014).
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).
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).
Krishnan, Y., Bathe, M. Designer nucleic acids to probe and program the cell. Trends in Cell Biology, 22: 624-633 (2012).
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).