Heddle Initiative Research Unit

In Nature, proteins have evolved to carry out a vast array of roles from DNA replication to muscle contraction. Imagine if we could build our own proteins to carry out specific tasks. Because of their small size, such proteins could find uses in many areas from electronics to smart drugs. However, designing protein structures de novo is not feasible and our approach involves modifying existing proteins so that they form new structures. With this goal in mind, we are carrying out basic nanoscience research into engineering proteins (and DNA) to build a toolbox of increasingly complex and functional structures. We will use these structures to build prototype self-assembled devices. Secondly we are interested in developing new therapeutics for use in treating bacterial infections and cancer. Our main target is DNA gyrase and other topoisomerases and we are currently investigating two potential inhibitor molecules. Finally we are interested in aging. We are interested both in the theory of aging, for which we are currently developing some hypothesis, and also the mechanisms of aging which we are investigating through calorie restriction experiments in Drosophila.

Research Subjects

• Precise Programming of the Size of a Self-Assembled Protein and DNA Structures
• Modified Proteins as Templates for Mineralization of Quantum Dots and Wires
• Structural Studies of Natural and Artificial Self-Assembled Proteins
• Theory and Mechanism of Aging
• Topoisomerases as Therapeutic Targets

Publications

1. Heddle, J.G., Yokoyama, T., Yamashita, I., Park, S.Y., and Tame, J.R.H.:
   "Rounding Up: Engineering 12-membered rings from the cyclic 11-mer TRAP."
   Structure 14, 925-33(2006)
   
2. Heddle, J. G., Fujiwara, I., Yamadaki, H., Yoshii, S., Nishio, K., Addy, C., Yamashita, I. and Tame, J. R. H.:
   "Using the Ring-Shaped Protein TRAP to Capture and Confine Gold Nanodots on a Surface."
   Small 3, 1950-1956(2007)
3. Heddle, J.G.:
   "Protein Cages, Rings and Tubes: Useful Components of Future Nanodevices?"
   Nanotechnology, Science and Applications 1, 67-78(2008)
4. Watanabe, M., Heddle, J.G, Unzai, S., Akashi, S., Park, S.Y., and Jeremy R.H. Tame.:
   "Nature of the TRAP:Anti-TRAP complex revealed by symmetry remodeling."
   Proc. Nat. Acad. Sci. USA 106, 2176-81(2009)
5. Frederico F., Miranda, Iwasaki, K., Yamashita, I., Jeremy, R. H., Tame, and Heddle, J.G.:
   "A self-assembled protein nanotube with a high aspect ratio."
   Small. 5, 2077-2084(2009)
   
6. Malay, A. D., Watanabe, M., Heddle, J. G. & Tame, J. R. H.:
   "Crystal structure of unliganded TRAP: implications for dynamic allostery"
   Biochem. J. 434, 429-434 (2011)
7. Malay, A. D., Heddle, J. G., Tomita, S., Iwasaki, K., Miyazaki, N., Sumitomo, K., Yanagi, H., Yamashita, I. & Uraoka, Y.
   "Gold Nanoparticle-Induced Formation of Artificial Protein Capsids"
   Nano Lett., 12, 2956-2059 (2012)
8. Trindade, L. S., Balduino, A., Aigaki, T. & Heddle, J. G.:
   "Senemorphism: a novel perspective on aging patterns and its implication for diet-related biology."
   Biogerontology 13, 457-466 (2012)
9. Trindade, L. S., Aigaki, T., Peixoto, A. A., Balduino, A., da Cruz, I. B. Mânica & Heddle, J. G.:
   "A novel classification system for aging theories. "
   Frontiers in Genetics 4, doi:10.3389/fgene.2013.00025. (2013)
10. Voet, A., Banwell, E. F., Sahu, K.K., Heddle, J.G., Zhang, K. Y. J.:
    "Protein interface pharmacophore mapping tools for small molecule protein:protein interaction inhibitor discovery."
    Curr. Topics Med. Chem., In the press