Research

Molecular basis for activation of immune system with recognition of microbial glycoconjugates

The Project Leader's Profile

Yukari Fujimoto

Associate Professor, Department of Chemistry, Graduate School of Science, Osaka University.

In 1989, graduated from Department of Chemistry, Faculty of Science, Osaka University. After industrial experience at Sumitomo Chemical and post-graduate studies at Columbia University, she received her Ph. D. from Osaka University in 2002. After postdoctoral studies at Nagoya University, she joined the faculty of Osaka University as an Assistant Professor in 2003, and then appointed as a Lecturer/Associate Professor in 2006. Since 2008, she holds the current position. Specialized in bioorganic chemistry and glycochemistry. Her current major interest is in the area of synthesis and function of bacterial glycoconjugates. She has received the Incentive Award in Synthetic Organic Chemistry, Japan.

Project Leader
  • Yukari Fujimoto, Ph. D., Associate Professor, Department of Chemistry, Graduate School of Science, Osaka University.
Research Members
  • Koichi Fukase, Ph. D., Professor, Department of Chemistry, Graduate School of Science, Osaka University.
  • Katsunori Tanaka, Ph. D., Assistant Professor, Department of Chemistry, Graduate School of Science, Osaka University.
  • Masaki Sato, Ph. D., Postdoctral fellow, Department of Chemistry, Graduate School of Science, Osaka University.

Summary

The detection of invading microorganism and activation of immune system with recognition of  microbial components are based on the cooperation of the organelle system. We have investigated the activation system with the chemically synthesized bacterial innate immunostimulatory glycoconjugates/lipoconjugates, which include the partial structures and also the labeled compounds as molecular probes. We have also developed chemical methods for the analysis of the molecular function in the organelle system.
As a common and particular structure in bacteria, we have synthesized bacterial cell wall peptidoglycan (PGN) fragments and constructed the compound library, and shown the detailed recognized structures by its intracellular receptors Nod1 and Nod2. We were also able to obtain potent Nod1 ligands with several hundred times more active than original structure, which enabled us to observe the in vivo function of Nod1.  
As for strong immunostimulating lipopolysaccharide from cell surface of Gram-negative bacteria, we also succeeded in developing new synthetic methods, which are essential for obtaining comprehensive chemical structures of lipid A's. We have also found an effective labeling method for the lipid A with keeping its bioactivities. The combination of the strategy of the lipid A synthesis and the labeling method will contribute to create functional molecules to analyze the immunoactivating system.

fujimoto.jpg We develop the synthetic method and investigate mechanisms of immunoactivation in organelle system using with the chemically synthesized immunostimulatory compounds library, which would lead to the basis for prevention and treatment of related diseases.

Some of Recent Papers

  1. Kawasaki A, Karasudani Y, Otsuka Y, Hasegawa M, Inohara N, Fujimoto Y, Fukase K. Synthesis of diaminopimelic acid-containing peptidoglycan fragments and tracheal cytotoxin (TCT) for investigation of their biological functions. Chem. Eur. J., 14, 10318-10330, 2008.
  2. Hasegawa M, Kawasaki A, Yang K, Fujimoto Y, Masumoto J, Breukink E, Nunez G, Fukase K, Inohara N. A role of lipophilic peptidoglycan-related molecules in induction of Nod1-mediated immune responses. J. Biol. Chem., 282, 11757-11764, 2007.
  3. Fujimoto Y, Iwata M, Imakita N, Shimoyama A, Suda Y, Kusumoto S, Fukase K. Synthesis of immunoregulatory Helicobacter pylori lipopolysaccharide partial structures. Tetrahedron Lett.,  48, 6577-6581, 2007.
  4. Fujimoto Y, Inamura S, Kawasaki A, Shiokawa Z, Shimoyama A, Hashimoto T, Kusumoto S, Fukase K. Chemical synthesis of peptidoglycan fragments for elucidation of the immunostimulating mechanism. J. Endotoxin Research, 13, 189-196, 2007.
  5. Inamura S, Fujimoto Y, Kawasaki A, Shiokawa Z, Woelk E, Heine H, Lindner B, Inohara N, Kusumoto S, Fukase K. Synthesis of peptidoglycan fragments and evaluation of their biological activity. Org. Biomol. Chem., 4, 232-242, 2006.