Dissecting Host–Parasite Signalling Interfaces in Leishmania: Mechanistic Drivers of Virulence and Immune Evasion

About the Project

Leishmaniasis is a major neglected tropical disease affecting over one million people annually, with rising incidence in new regions including Southern Europe. Current treatments are limited by toxicity, cost, and increasing drug resistance, and no effective human vaccine exists. A key feature of Leishmania infection is its ability to survive within host macrophages by suppressing immune responses; however, the underlying molecular mechanisms remain poorly defined.

This PhD project will investigate how Leishmania manipulates host cell signalling to drive virulence and immune evasion, focusing on parasite surface ecto-enzymes (ecto-phosphatases and ecto-nucleotidases). These enzymes hydrolyse extracellular nucleotides, enabling nutrient acquisition while suppressing host microbicidal responses, including nitric oxide production and inflammatory signalling.

Using in vitro macrophage infection models, the student will characterise the expression and activity of ecto-enzymes during infection, particularly in the clinically relevant amastigote stage. The project will then examine host signalling pathways altered during infection using phospho-proteomics, with emphasis on key immune pathways such as MAPK, NF-κB, and JAK/STAT.

Functional relevance will be established through chemical and genetic perturbation approaches to determine the role of specific ecto-enzymes in parasite survival, replication, and immune modulation.

This project offers a unique opportunity to develop cutting-edge skills in parasitology, omics technologies, and translational research. The findings will contribute to the identification of novel anti-virulence targets and may inform the development of new therapeutic and vaccine strategies. The project is aligned with a One Health perspective, recognising the broader relevance of Leishmania infections across human and animal health.

The successful candidate will join a supportive and dynamic research environment and receive comprehensive training in experimental design, data analysis, and scientific communication, preparing them for a career in academia, industry, or global health research.

Supervisors:
Dr Godwin Ebiloma
Professor Geoff Hide