Research Summary

Elucidating role of EhMAP kinase in growth and phagocytosis and identification of its substrates in E. histolytica

MAP kinases respond to extracellular stimuli (mitogens) and regulate various cellular activities including growth and phagocytosis via an evolutionary conserved MAP Kinase signalling cascade. Inside a human host E. histolytica interact with endothelial cells and extracellular matrix (ECM) components via many known amoebic surface receptors. This receptor mediated signalling is known to activate Rho family of small GTPases resulting in reorganization of the actin cytoskeleton and the release of proteases which facilitates locomotion and propagation of the invading trophozoites. All these studies strongly suggest that a signalling pathway, similar to the one used in mammalian cells, is activated when E. histolytica trophozoites adhere to mammalian intestinal cells.

Unlike mammals where three MAP kinases (p38, ERK and JNK) are well studied, Entamoeba contains only one MAP kinase homolog (EhMAPK) which is similar to mammalian ERK2. Since, virtually nothing is known about EhMAPK signalling cascade in E. histolytica, this study will fill a clinically relevant scientific knowledge gap. We are using various cellular and biochemical techniques to elucidate the upstream regulators and downstream targets of EhMAPK pathway. We are utilizing both in vivo and in vitro models along with various microscopy and proteomics methodologies to achieve mentioned goals. In conclusion, our finding may elucidate how the MAP kinase pathway in E. histolytica responds to environmental factors and how this signalling modulates some of the biological processes.