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 the 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, which 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 characterisation of the innate immune system, not only in insects but also in vertebrates, studies on vector immunity have lagged.

The objective of the Gangloff Group is to contribute to the characterisation of the structure and function of mosquito immune receptors that are implicated in resistance to pathogens and which have undergone gene duplication in disease-carrying mosquitoes. Our multidisciplinary approach will contribute to a better understanding in mosquito immunity, which may have acquired new functions relating to host-pathogen homeostasis compared to other insects.

Research objectives

• Structural characterisation of duplicated immune receptors.

• Structural characterisation of the mechanism of ligand binding and activation of immune receptors.

• Ligand fishing for orphan receptors.

• Determination of structure-function relationships in cell-based assays.

• Imaging of the cellular compartmentalisation of signalling.

Key publications

West C, Rus F, Chen Y, Kleino A, Gangloff M, Gammon DB, Silverman N (2019). IIV-6 inhibits NF-κB responses in Drosophila. Viruses, 11(5):E409. doi: 10.3390/v11050409

de Groot AM, Thanki K, Gangloff M, Falkenberg E, Zeng X, van Bijnen DCJ, van Eden W, Franzyk H, Nielsen HM, Broere F, Gay NJ, Foged C, Sijts AJAM (2018). Immunogenicity testing of lipidoids in vitro and in silico: modulating lipidoid-mediated TLR4 activation by nanoparticle design. Mol. Ther. Nucleic Acids, 11:159-169. doi: 10.1016/j.omtn.2018.02.003

Kleino A, Ramia NF, Bozkurt G, Shen Y, Nailwal H, Huang J, Napetschnig J, Gangloff M, Chan FK, Wu H, Li J, Silverman N (2017). Peptidoglycan-sensing receptors trigger the formation of functional amyloids of the adaptor protein Imd to initiate Drosophila NF-κB signaling. Immunity, 47(4):635-647. doi: 10.1016/j.immuni.2017.09.011

Foldi I, Anthoney N, Harrison N, Gangloff M, Verstak B, Nallasivan MP, AlAhmed S, Zhu B, Phizacklea M, Losada-Perez M, Moreira M, Gay NJ, Hidalgo A (2017). Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. J. Cell Biol., 216(5):1421-1438. doi: 10.1083/jcb.201607098

Lewis M, Arnot CJ, Beeston H, McCoy A, Ashcroft AE, Gay NJ, Gangloff M (2013). 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(51):20461-20466. doi: 10.1073/pnas.1317002110