Monique Gangloff

Structural Biology of Mosquito Immunity

Vector-borne diseases are the source of over a billion infections and a million deaths annually according to World Health Organization. Innate immunity plays a key role in the complex relationship between pathogen, vector and the vertebrate host. Pathogens have evolved to survive in the different environments presented by arthropod vectors and vertebrate hosts and this has resulted in microbial adaptation and divergence in immune system responses in both vector and host. Consequently, the study of the interactions between vectors and pathogens is essential for future development of novel control strategies against vector-borne diseases.

Mosquitoes are well-known disease vectors. They transmit a number of life-threatening diseases such as malaria and dengue fever. While the fruit fly, Drosophila melanogaster has been a model system for the characterization of the innate immune system not only in insects, but also in vertebrates, studies on vector immunity has lagged.

Our objective is to contribute to the characterization of the structure and function of mosquito immune receptors that are implicated in resistance to pathogens and have undergone gene duplication in disease-carrying mosquitoes. Our specific aims are the following:

Structural characterization of duplicated immune receptors
Structural characterization of their mechanism of ligand binding and activation
Ligand fishing for orphan receptors
Structure-function relationships in cell-based assays
Imaging of the cellular compartmentalization of signalling

Our multidisciplinary approach will contribute to a better understanding in mosquito immunity that may have acquired new functions relating to host-pathogen homeostasis compared to other insects.

Contact Details

Department of Biochemistry
University of Cambridge
80 Tennis Court Road
Cambridge CB2 1GA
UK
Tel: +44 (0)1223 766 042
Email: mg308@cam.ac.uk

Collaborators

Prof. Nick J. Gay
Prof. Clare E. Bryant
Prof. J.M. Ruyscchaert
Prof. C. Foged
Dr. A. Hidalgo

Recent publications

Foldi, I. et al. Three-tier regulation of cell number plasticity by Tolls and neurotrophins in Drosophila. JCB (In press).

Pizzuto M. et al. Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers. J Control Release. 247:182-193 (2017).

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).

Gay, N. J. et al. Assembly and localization of Toll-like receptor signalling complexes. Nat. Rev. Immunol. 14, 546–558 (2014).

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 Spätzle 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).

Herre, J. et al. Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances TLR activation by lipid ligands. J. Immunol. 191, 1529–35 (2013).