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Dr Monique Gangloff

Dr Monique  Gangloff

Senior Research Associate

Innate immunity

Molecular and structural biology

Monique Gangloff is available for consultancy.


Research Interests

I am interested in proteins of medical importance such as estrogen nuclear receptors, targeted by antiestrogens to fight breast cancer, and Toll-like receptors (TLRs), which are key regulators of innate and adaptive immune responses, as well as molecular triggers of a number of diseases, including sepsis, immunodeficiencies, allergies and cancer. More recently, I have added another fascinating target to my repertoire with Leucine-Rich Repeat Kinase 2 (LRRK2), whose variants cause genetically inherited Parkinson’s disease.

 

My background is in molecular and structural biology, in particular X-ray crystallography. My research interests lie at the intersection between structural biology and signal transduction with the aim of understanding the molecular mechanisms of receptor-ligand interactions and activation of intracellular signalling pathways with atomic details.

 

I enjoy collaborative work and have successfully used protein modelling and docking to unravel the activation mechanism of mammalian TLR4 in collaboration with Professor Clare Bryant, whose approach is to gain insight in innate immunity based on its species-specific response to molecular patterns of microbial origin. I am also interested in clarifying the mode of action of non-canonical TLR ligands, such as cationic lipids developed for gene therapy and vaccine adjuvancy. This work is done in collaboration with Professors Jean-Marie Ruysschaert and Camilla Foged.

 

I combine structural techniques (X-ray crystallography and electron microscopy) with biophysical tools and bioinfomatics to understand the mechanism of Drosophila TOLL signalling during development and in adult life, in both the innate immune and nervous systems. I tackle functional aspects of insect Toll signalling in collaboration with Professors Jean-Luc Imler, Alicia Hidalgo and Neil Silverman.

 

Ultimately, I want to explore the structure-function relationships in insect and mammalian species to learn about the fascinating mechanisms of protein network evolution.

Key Publications

  • Lonez, C. et al. Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface. Cell. Mol. Life Sci. 72, 3971–3982 (2015).
  • Irvine, K. L. et al. Identification of key residues that confer Rhodobacter sphaeroides LPS activity at horse TLR4/MD-2. PLoS One 9, (2014).
  • Lewis, M. et al. Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation. Proc. Natl. Acad. Sci. U. S. A. 110, 20461–6 (2013).
  • Gangloff, M. et al. J. Liesegang-like patterns of Toll crystals grown in gel. J. Appl. Crystallogr. 46, 337–345 (2013).
  • Gangloff, M. Different dimerisation mode for TLR4 upon endosomal acidification? Trends Biochem. Sci. 37, 92–98 (2012).
  • Walsh, C. et al. Elucidation of the MD-2/TLR4 Interface Required for Signaling by Lipid IVa. J. Immunol. 181, 1245–1254 (2008).
  • Gay, N. J. & Gangloff, M. Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76, 141–165 (2007).
  • Gangloff, M. et al. Crystal Structure of a Mutant hERalpha Ligand-binding Domain Reveals Key Structural Features for the Mechanism of Partial Agonism. J. Biol. Chem. 276, 15059–15065 (2001).