All Publications

  • CD22 blockade restores homeostatic microglial phagocytosis in ageing brains NATURE Pluvinage, J. V., Haney, M. S., Smith, B. H., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., Shuken, S. R., Gate, D., Scott, M., Khatri, P., Luo, J., Bertozzi, C. R., Bassik, M. C., Wyss-Coray, T. 2019; 568 (7751): 187-+
  • Ladderane phospholipids form a densely packed membrane with normal hydrazine and anomalously low proton/hydroxide permeability. Proceedings of the National Academy of Sciences of the United States of America Moss, F. R., Shuken, S. R., Mercer, J. A., Cohen, C. M., Weiss, T. M., Boxer, S. G., Burns, N. Z. 2018


    Ladderane lipids are unique to anaerobic ammonium-oxidizing (anammox) bacteria and are enriched in the membrane of the anammoxosome, an organelle thought to compartmentalize the anammox process, which involves the toxic intermediate hydrazine (N2H4). Due to the slow growth rate of anammox bacteria and difficulty of isolating pure ladderane lipids, experimental evidence of the biological function of ladderanes is lacking. We have synthesized two natural and one unnatural ladderane phosphatidylcholine lipids and compared their thermotropic properties in self-assembled bilayers to distinguish between [3]- and [5]-ladderane function. We developed a hydrazine transmembrane diffusion assay using a water-soluble derivative of a hydrazine sensor and determined that ladderane membranes are as permeable to hydrazine as straight-chain lipid bilayers. However, pH equilibration across ladderane membranes occurs 5-10 times more slowly than across straight-chain lipid membranes. Langmuir monolayer analysis and the rates of fluorescence recovery after photobleaching suggest that dense ladderane packing may preclude formation of proton/hydroxide-conducting water wires. These data support the hypothesis that ladderanes prevent the breakdown of the proton motive force rather than blocking hydrazine transmembrane diffusion in anammox bacteria.

    View details for PubMedID 30150407

  • Ladderane phospholipids form dense, low-polarity membranes with low proton/hydroxide permeability Moss, F., Shuken, S., Mercer, J., Cohen, C., Weiss, T., Burns, N., Boxer, S. AMER CHEMICAL SOC. 2018
  • Ladderane Phospholipids Form Dense Membranes with Low Proton Permeability Moss, F. R., Shuken, S. R., Mercer, J. M., Cohen, C. M., Burns, N. Z., Boxer, S. G. CELL PRESS. 2018: 260A
  • Chemical Synthesis and Self-Assembly of a Ladderane Phospholipid JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Mercer, J. A., Cohen, C. M., Shuken, S. R., Wagner, A. M., Smith, M. W., Moss, F. R., Smith, M. D., Vahala, R., Gonzalez-Martinez, A., Boxer, S. G., Burns, N. Z. 2016; 138 (49): 15845-15848


    Ladderane lipids produced by anammox bacteria constitute some of the most structurally fascinating yet poorly studied molecules among biological membrane lipids. Slow growth of the producing organism and the inherent difficulty of purifying complex lipid mixtures have prohibited isolation of useful amounts of natural ladderane lipids. We have devised a highly selective total synthesis of ladderane lipid tails and a full phosphatidylcholine to enable biophysical studies on chemically homogeneous samples of these molecules. Additionally, we report the first proof of absolute configuration of a natural ladderane.

    View details for DOI 10.1021/jacs.6b10706

    View details for Web of Science ID 000389962800013

    View details for PubMedID 27960308

    View details for PubMedCentralID PMC5279923