Research Focus

Our research is focused in two areas: the structure and function of the cytoskeleton and miniaturized ultra-fast bioanalytical devices.

Cytoskeleton Bundles of actin filaments support finger-like projections of the cell membrane. Our lab studies the structure and function of villin, fimbrin, and scruin, three proteins that crosslink actin into bundles. The research includes structural studies using NMR spectroscopy, cryoelectron microscopy, and x-ray diffraction, cell biology studies using GFP-tagged wild-type and mutant proteins and 4D light microscopy, biophysical studies of protein folding and large-scale conformational changes of bundles. The major findings from our research include a complex of fimbrin and vimentin that plays a potential role in organizing the actin and vimentin cytoskeletons, preliminary measurements of the forces involved in the spring-like movement of the acrosomal process, an atomic fit of fimbrin on actin, and a 3D reconstruction of an actin bundle.

BioMEMS Ultrafast analysis of DNA is vital for genotyping and sequencing applications. In our lab, we have designed, constructed, and tested microelectrophoresis devices capable of 1 minute genotyping and 1 hour sequencing. Our experience in merging microfabrication, molecular biology, and systems integration is being applied to biosensors constructed from arrays of DNA and proteins

Selected Publications

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Sun, S., Footer, M., and Matsudaira, P.T. Modification of Cys-837 Identifies an Actin-binding Site in the B-Propeller Protein Scruin. Molec. Biol. of the Cell 8:421-430 (1997).

Goldsmith, S., Pokala, N., Shen, W., Fedorov, A.A., Matsudaira, P.T., and Almo, S.A. The Structure of an Actin-crosslinking Domain from Human Fimbrin. Nature Struct. Biol. 4:708-712 (1997).

Schmalzing, D., Koutny, L., Adourian, A., Belgrader, P., Matsudaira, P.T., and Ehrlich, D.J. DNA Typing in Thirty Seconds with a Microfabricated Device, PNAS 94:10273-10278 (1997).

Hanein, D., Volkmann, N., Goldsmith, S., Michon, A-M., Lehman, W., Craig, R., DeRosier, D., Almo, S., and Matsudaira, P.T., An Atomic Model of Fimbrin binding to F-actin and It's Implications for Filament Crosslinking and Regulation. Nature Struct. Biol. 5:787-792 (1998).

Sherman, M.B., Jakana, J., Sun, S., Matsudaira, P.T., Chiu, W. and Schmid, M.F., The Three-Dimensional Structure of a Dynamic Actin Bundle, the Limulus Acrosomal Process. J. Mol. Biol. 294:139-149 (1999).

Ehrlich, D.J., and Matsudaira, P.T. Microfluidic Devices for DNA Analysis. Trends in Biotechnology 17:315-319 (1999).

Correia, I., Chu, D., Chou, Y-H., Goldman, R.D., and Matsudaira, P.T. Integrating the Actin and Vimentin Cytoskeletons: Adhesion-dependent Formation of Fimbrin-vimentin Complexes in Marophages. J. Cell Biol. 128:831-842 (1999).

Lodish, Berk, Zipursky, Matsudaira, Baltimore, and Darnell. Molecular Biology of the Cell, 4th edition, W.H.Freeman (1999).

Schmalzing, D., Belenky, A., Novotny, M.A., Koutny, L., Salas-Solano, O., El-Difrawy, S., Adourian, A., Matsudaira, P., and Ehrlich, D. Microchip Electrophoresis: A Method for High-Speed SNP Detection, Nucleic Acid Research 28:e43 (2000).

Mahadevan, L., Matsudaira, P. Motility Powered by Supramolecular Springs and Ratchets, Science 288:95-99 (2000).

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