Unravelling the immunology of complex glycolipids by chemical synthesis
Grant number: DP160100597 | Funding period: 2016 - 2019
This project seeks to develop new approaches to chemically synthesise bacterial and fungal glycolipids and develop a molecular-level understanding of their effect on the immune system. Bacterial and fungal glycolipids are exotic chemical species that act as danger signals to prime and modulate our innate immune responses. These complex glycolipids possess powerful immunological activities that continue to shape our understanding of innate immunity, yet cannot be acquired from natural sources in the quantities and purity needed. The approaches expected to be developed in the project will be used to illuminate molecular details of immune signalling through pattern recognition receptors and pre..View full description
Related publications (19)
Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors
Masahiro Nagata, Kenji Toyonaga, Eri Ishikawa, Shojiro Haji, Nobuyuki Okahashi, Masatomo Takahashi, Yoshihiro Izumi, Akihiro Imamura, Koichi Takato, Hideharu Ishida, Shigenori Nagai, Petr Illarionov, Bridget L Stocker, Mattie SM Timmer, Dylan GM Smith, Spencer J Williams, Takeshi Bamba, Tomofumi Miyamoto, Makoto Arita, Ben J Appelmelk
Helicobacter pylori causes gastritis, which has been attributed to the development of H. pylori-specific T cells during infection...
Candida albicans steryl 6-O-acyl-alpha-d-mannosides agonize signalling through Mincle
Tram Nguyen, Yuki Hosono, Takashi Shimizu, Sho Yamasaki, Spencer J Williams
The C-type lectin receptor Mincle binds Candida albicans and has been implicated in its pathobiology, but the molecular effectors ..
Cholesteryl 6-O-acyl-alpha-glucosides from diverseHelicobacterspp. signal through the C-type lectin receptor Mincle
Dylan GM Smith, Emi Ito, Sho Yamasaki, Spencer J Williams
Helicobacter spp. are Gram-negative bacteria that cause a spectrum of disease in the gut, biliary tree and liver. Many Helicobacte..
Design of potent Mincle signalling agonists based on an alkyl beta-glucoside template
Dylan GM Smith, Yuki Hosono, Masahiro Nagata, Sho Yamasaki, Spencer J Williams
The innate immune receptor Mincle senses lipid-based molecules derived from pathogens, commensals and altered self. Based on emerg..
alpha-Glucuronosyl and alpha-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi
Satvika Burugupalli, Catarina F Almeida, Dylan GM Smith, Sayali Shah, Onisha Patel, Jamie Rossjohn, Adam P Uldrich, Dale I Godfrey, Spencer J Williams
Natural killer T cells express T cell receptors (TCRs) that recognize glycolipid antigens in association with the antigen-presenti..
Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors
Catarina F Almeida, Srinivasan Sundararaj, Jerome Le Nours, T Praveena, Benjamin Cao, Satvika Burugupalli, Dylan GM Smith, Onisha Patel, Manfred Brigl, Daniel G Pellicci, Spencer J Williams, Adam P Uldrich, Dale I Godfrey, Jamie Rossjohn
Type I and type II natural killer T (NKT) cells are restricted to the lipid antigen-presenting molecule CD1d. While we have an und..
Distortion of mannoimidazole supports a B-2,B-5 boat transition state for the family GH125 alpha-1,6-mannosidase from Clostridium perfringens
Alexandra Males, Gaetano Speciale, Spencer J Williams, Gideon J Davies
Enzyme transition-state mimics can act as powerful inhibitors and allow structural studies that report on the conformation of the ..
A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites
M Fleur Sernee, Julie E Ralton, Tracy L Nero, Lukasz F Sobala, Joachim Kloehn, Marcel A Vieira-Lara, Simon A Cobbold, Lauren Stanton, Douglas EV Pires, Eric Hanssen, Alexandra Males, Tom Ward, Laurence M Bastidas, Phillip L van der Peet, Michael W Parker, David B Ascher, Spencer J Williams, Gideon J Davies, Malcolm J McConville
Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is compose..
Synthetic beta-1,2-Mannosyloxymannitol Glycolipid from the Fungus Malassezia pachydermatis Signals through Human Mincle
Phillip L van der Peet, Christian Gunawan, Miyuki Watanabe, Sho Yamasaki, Spencer J Williams
Mincle is a C-type lectin receptor of the innate immune system with the ability to sense pathogens and commensals through lipidic ..
Eucalyptus subgenus Eucalyptus (Myrtaceae) trees are abundant sources of medicinal pinocembrin and related methylated flavanones
Jason QD Goodger, Samiddhi L Senaratne, Phillip van der Peet, Rhys Browning, Spencer J Williams, Dean Nicolle, Ian E Woodrow
Plant-derived flavanones such as pinocembrin and related methylated forms are of interest for their potential medicinal use. Comme..
Total synthesis and mass spectrometric analysis of a Mycobacterium tuberculosis phosphatidylglycerol featuring a two-step synthesis of (R)-tuberculostearic acid
Satvika Burugupalli, Mark B Richardson, Spencer J Williams
We report the total synthesis of (R)-tuberculostearic acid-containing Mycobacterium tuberculosis phosphatidylglycerol (PG). The ap..
Gas-Phase Intercluster Thiyl-Radical Induced C-H Bond Homolysis Selectively Forms Sugar C2-Radical Cations of Methyl D-Glucopyranoside: Isotopic Labeling Studies and Cleavage Reactions
Sandra Osburn, Gaetano Speciale, Spencer J Williams, Richard AJ O'Hair
A suite of isotopologues of methyl D-glucopyranosides is used in conjunction with multistage mass spectrometry experiments to dete..
Selective Manipulation of Discrete Mannosidase Activities in the Endoplasmic Reticulum by Using Reciprocally Selective Inhibitors
Taiki Kuribara, Makoto Hirano, Gaetano Speciale, Spencer J Williams, Yukishige Ito, Kiichiro Totani
Within the endoplasmic reticulum, immature glycoproteins are sorted into secretion and degradation pathways through the sequential..
Quantitation in the regioselectivity of acylation of glycosyl diglycerides: total synthesis of a Streptococcus pneumoniae alpha-glucosyl diglyceride
Mark B Richardson, Dylan GM Smith, Spencer J Williams
The fidelity of acylation regioselectivity in the synthesis of mixed glycosyl diacylglycerols can be accurately measured by quanti..
Total Synthesis of Mycobacterium tuberculosis Dideoxymy-cobactin-838 and Stereoisomers: Diverse CD1a-Restricted T Cells Display a Common Hierarchy of Lipopeptide Recognition
Janice MH Cheng, Ligong Liu, Daniel G Pellicci, Scott JJ Reddiex, Rachel N Cotton, Tan-Yun Cheng, David C Young, Ildiko Van Rhijn, D Branch Moody, Jamie Rossjohn, David P Fairlie, Dale I Godfrey, Spencer J Williams
Mycobacterium tuberculosis produces dideoxymycobactin-838 (DDM-838), a lipopeptide that potently activates T cells upon binding to..
Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle
Phillip L van der Peet, Masahiro Nagata, Sayali Shah, Jonathan M White, Sho Yamasaki, Spencer J Williams
Mincle (macrophage-inducible C-type lectin) is a C-type lectin receptor that provides the capacity for immune sensing of a range o..
Total synthesis of a cyclopropane-fatty acid alpha-glucosyl diglyceride from Lactobacillus plantarum and identification of its ability to signal through Mincle
Sayali Shah, Masahiro Nagata, Sho Yamasaki, Spencer J Williams
We report a concise synthesis of glycolipid GL1 from Lactobacillus plantarum commencing from methyl α-d-glucopyroside. A Jacobsen ..