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.
Applications for post-doc positions are welcome.
Department of Biochemistry
University of Cambridge
80 Tennis Court Road
Cambridge CB2 1GA
Tel: +44 (0)1223 766 042
Thank, K. et al. Immune reactions in the delivery of RNA interference-based therapy: Mechanisms and opportunities. Pan Stanford series on Clinical Nanomedicine (Volume 3, Bookchapter 14. In press)
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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).