A primary focus of the Taylor lab is to understand the molecular architecture and functional interactions that regulate human telomeres and telomerase. We are particularly interested in understanding how the telomere is assembled and how it interacts with telomerase to regulate its function. Another primary area of research in my lab addresses how telomere end-binding proteins interact exclusively with telomere DNA to prevent illicit induction of the DNA damage response. An overarching goal is to use the detailed, mechanistic insight to design small molecules that can be used to manipulate processes related to telomeres and telomerase in cancer cells. An NIH Innovator Award has provided the primary funding for achieving this latter objective.
An equally important emphasis within my research group lies in the structural determination of nucleoprotein complexes. My lab has used cryo-electron microscopy to examine the structural architecture of cellular assemblies that are important for DNA packaging, mRNA 3’ processing, ribosome-mediated protein translation, membrane transport, and virus structure, assembly, and maturation. The structural detail helps to understand the molecular mechanisms involved in important cellular pathways and provides information for how they become abrogated in disease states such as cancer. We are using this information to repurpose and develop small molecule compounds that are intended to exploit or manipulate these properties as potential therapies. Ongoing projects are aimed to understand protein phosphatase 2A biogenesis, structure, and selective substrate binding; cap-independent mechanisms of protein synthesis; and assembly and maturation of the anthrax toxin membrane-spanning pore.
Regulation – and deregulation – of gene expression are critical events for every process within the cell. Alteration of these intricate processes, for example as consequences of genetic defects or bacterial/viral infections, can readily lead to one of many human ailments. The control of these processes is commonly modulated by multi-protein complexes; in fact, proteins rarely act alone, but interact intimately and precisely with other proteins and nucleic acids to properly perform their cellular functions. My laboratory studies the structure and molecular mechanisms of macromolecular machines involved in DNA maintenance and RNA maturation and biogenesis. We use cryo-electron microscopy and single particle reconstruction techniques as a primary tool for visualizing these complexes and, thus, to better understand their functions.
- Corriveau, M., Mullins, M.R., Baus, D., Harris, M.E., & Taylor, D.J. (2013) Coordinated Interactions of Multiple POT1-TPP1 Proteins with Telomere DNA. J. Biol. Chem. In Press.
- Tsybovsky, Y., Orban, T., Molday, R.S., Taylor, D., & Palczewski, K. (2013) Molecular organization and ATP-induced conformational changes of ABCA4, the photoreceptor-specific ABC transporter. Structure, 21:854-860.
- Lobo, G.P., Amengual, J., Baus, D., Shivdasani, R.A., Taylor, D., & von Lintig, J. (2013) Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX. J. Biol. Chem., 288:9017-9027.
- Taylor, D.*, Unbehaun, A., Li, W., Das, W., Lei, S., Lao, H., Grassucci, R.A., Pestova, T.V., & Frank, J. (2012) Cryo-EM structure of the mammalian eRF1- eRF3-associated termination complex. Proc Natl Acad Sci U S A, 109:18413-8.
- Krokowski, D., Gaccioli, F., Majumder, M., Mullins, M.R., Yuan, C.L., Papadopoulou, B., Merrick, W.C., Komar, A.A., Taylor, D., & Hatzaglou, M. (2011) Characterization of hibernating ribosomes in mammalian cells. Cell Cycle. 10(16):1-12.
- Taylor, D.J., Podell, E.R., Taatjes, D.J., & Cech, T.R. (2011) Multiple POT1-TPP1 proteins coat and compact long telomeric single-stranded DNA. J. Mol. Biol. 2011. 410:10-17.
- Speir, J.A., Taylor, D.J., Natarajan, P., Pringle, F.M., Ball, L.A. & Johnson J. E. (2010) Evolution in Action: N and C Termini of Related T=4 Viruses Exchange Roles as Molecular Switches. Submitted to Structure.
- Taylor, D. J., Devkota, B., Huang, A., Topf, M., Narayanan, E., Sali, A., Harvey, S., & Frank, J. (2009) Comprehensive Molecular Structure of the Eukaryotic Ribosome. Structure. 17:11591-1604
- Shi, Y., Campigli Di Giammartino,D., Taylor, D., Sarkeshik, A., Rice, W.J., Yates III, J.R., Frank, J., & Manley, J.L. (2009) Molecular Architecture of the Human pre-mRNA 3’ Processing Complex. Mol. Cell. 33:365-376.
- Grassucci, R. A.,Taylor, D. J., and Frank, J. (2008) Preparation of macromolecular complexes for cryo-electron microscopy. Nat Protoc. 2007;2(12):3239-46.
- Grassucci, R. A.,Taylor, D. J., and Frank, J. (2007) Visualization of Macromolecular Complexes Cryo- Electron Microscopy with FEI Tecnai TEMs. Nat Protoc. 2:3239-3246.
- Frank, J., Gao, H., Sengupta, J., Gao, N., andTaylor, D.J. (2007) The process of mRNA-tRNA Translocation. Proc Natl Acad Sci U S A, 104:19671-8.
- Taylor, D.J., Nilsson, J., Merrill, A.R., Andersen, G.R., Nissen, P., and Frank, J. (2007) Structures of modified eEF2•80S ribosome complexes reveals the role of GTP hydrolysis in translocation. EMBO J. 26: 2421 – 2431.