Spatial genomic tools to target parasite transmission
Supervisor: Dr Virgina Howick, School of Biodiversity, One Health & Veterinary Medicine
Background: Insect disease vectors pose a huge burden to global public health. For example, Anopheles mosquitoes, which transmit malaria, kill over 600,000 people each year. Understanding how insects transmit disease is essential for increasing the repertoire of control measures. However, because insects are small, studies that resolve how parasites transit through vector tissues and how insect cells respond have comparatively lagged behind mammalian systems. These interactions depend on fine-scale molecular variation in host tissues, but we do not know how tissue regionalisation and cellular-composition impact infection outcomes. Recent technological advances in spatial transcriptomics have opened the door to start to dissect these processes.
Approach: A critical bottleneck in the malaria parasite life cycle is the transition from ingested blood across the midgut: parasites that do not make this transition do not survive to transmit. We have used single-cell genomic tools in the malaria parasite, in combination with genetics and phenotypic assays to reveal development at high resolution in the parasite, as well as mosquito cell-type specific responses. Having shown the molecular diversity of these processes, it is now critical to show how they are arranged spatially. This project will use spatial transcriptomic approaches to investigate (1) how cellular composition varies across the midgut regions, (2) what cell-types are invaded by the parasite, and (3) how perturbation from infection and contact with the parasite changes gene expression in Anopheles mosquitoes.